JPH0597819A - N-(3,3-bisubstituted acryloyl) piperazine derivative - Google Patents

Abstract

PURPOSE:To obtain a new piperazine derivative capable of becoming a therapeutic agent for various diseases considered to be related to PAF, having excellent blood activating factor (PAF) antagonism. CONSTITUTION:A compound of formula I [R<1> and R<2> are R<6>, CH=CH2-R<6> or Cidentical=CH2-R<6> (R<6> is aryl or heteroaryl which may contain 1-5 substituent groups of group A); R<3> is H, alkyl, CN or R<6>; X is O or S; A is alkylene, CO, CS, SO or SO2; R<4> is phenyl which may contain 1-5 substituent groups of group A and Group B or heteroaryl which may contain 1-5 substituent groups of group A; R<5> is H, alkyl or R<5> and R<3> are bonded to form (CH2)p [(p) is 1-3)]; (m) and (n) are 1 or 2; group A is alkyl, alkoxy, OH, halogen, NO, etc. ; group B is alkylthio, alkylsulfinyl, etc.] such as 1-3[3,3-bis(4-methoxyphenyl) acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine. The compound is obtained by reaction following the reaction formula (B is group of formula II).

Description

Detailed Description of the Invention

[0001]

[Object of the Invention]

[0002]

TECHNICAL FIELD The present invention relates to a novel N- (3,3-disubstituted acryloyl) piperazine derivative having excellent antagonistic activity against platelet activating factor (PAF). PAF
Is an in-vivo ether-type phospholipid having a strong physiological action (platelet aggregation activating action, leukocyte activating action, blood pressure lowering action, etc.), and acts as one of the mediators of immune reaction, It is believed to be deeply involved in certain pathological conditions. Therefore, a substance having an antagonistic effect on PAF is PA
It can be used as a therapeutic drug for various diseases in which F is considered to be involved, for example, endotoxin shock, anaphylactic shock, nephritis, myocardial infarction, angina, asthma, psoriasis, gastric ulcer and the like. It can also be used as a preventive agent for rejection during organ transplantation.

[0003]

2. Description of the Related Art As a compound having a bis (aryl) methylene group, JP-A-64-85963 and JP-A-6-65963.
It is known that the compound described in JP-A No. 4-31766 and the compound described in JP-A No. 64-77 as a compound having a piperazine skeleton have a PAF antagonistic action.

[0004]

The present inventors have found that the PAF
As a result of many years of intensive research on the synthesis of a derivative having an antagonistic action and its pharmacological activity, a novel N- (3,3-disubstituted acryloyl) piperazine derivative having a structure different from that of a known compound was excellent. The present invention has been completed based on the finding that it has a PAF antagonistic effect, is less toxic, and that stable and high blood concentration can be obtained by oral administration.

[0005]

[Constitution of the invention]

[0006]

SUMMARY OF THE INVENTION The novel N- (3,3
-Di-substituted acryloyl) piperazine derivative has the general formula

[0007]

[Chemical 3]

[Wherein R ¹ and R ² are the same or different and each represents a group having the formula —R ⁶ [wherein, R ⁶ is an optionally substituted aryl group (the substituent is 1 to 5 substituents selected from the following Group A) or an optionally substituted heteroaryl group (the substituent is 1 to 5 substituents selected from the following Group A). Yes.). ]
A group having the formula —CH═CH—R ⁶ (wherein R ⁶ has the same meaning as described above) or a group having the formula —C≡C —R ⁶ (wherein
R ⁶ has the same meaning as described above. ) Is shown. R ³ represents a hydrogen atom, a lower alkyl group, a cyano group or a group having the formula —R ⁶ (in the formula, R ⁶ has the same meaning as described above), or, together with R ⁵ , formula - (CH _{2) p} - shows a (wherein, p is showing a 1 to 3.). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituents are 1 to 5 substituents selected from the following Group A and Group B) or an optionally substituted heteroaryl group. (The substituent is 1 to 5 selected from the following group A.
Are substituents. ) Is shown. R ⁵ represents a hydrogen atom or a lower alkyl group, or, together with R ³ ,
Formula - (CH _{2) p} - shows a (wherein, p is showing a 1 to 3.). m represents 1 or 2. n represents 1 or 2. Provided that R ⁴ represents a 3-pyridyl group, R ³ represents a hydrogen atom or a lower alkyl group, R ⁵ represents a hydrogen atom or a lower alkyl group, and m and n each represent ^1. And R ² are the same or different and each is a group having the formula —R ^{6 ′} , wherein R ^{6 ′} is a substituted aryl group (wherein the substituent is 1 to 5 selected from the following group A). Or a heteroaryl group which may be substituted (the substituents are 1 to 5 substituents selected from the following Group A). ] In groups (having the formula -CH = CH-R ^6,
R ⁶ has the same meaning as described above. ) Or a group having the formula —C≡C—R ⁶ (in the formula, R ⁶ has the same meaning as described above). }, And a preventive or therapeutic agent for a disease caused by PAF of the present invention has the general formula

[0009]

[Chemical 4]

[In the formula, R ¹ and R ² are the same or different and each is a group having the formula -R ⁶ [wherein R ⁶ is an optionally substituted aryl group (the substituent is 1 to 5 substituents selected from the following Group A) or an optionally substituted heteroaryl group (the substituent is 1 to 5 substituents selected from the following Group A). Yes.) ]
A group having the formula —CH═CH—R ⁶ (wherein R ⁶ has the same meaning as described above) or a group having the formula —C≡C —R ⁶ (wherein
R ⁶ has the same meaning as described above. ) Is shown. R ³ represents a hydrogen atom, a lower alkyl group, a cyano group or a group having the formula —R ⁶ (in the formula, R ⁶ has the same meaning as described above), or, together with R ⁵ , formula - (CH _{2) p} - shows a (wherein, p is showing a 1 to 3.). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituents are 1 to 5 substituents selected from the following Group A and Group B) or an optionally substituted heteroaryl group. (The substituent is 1 to 5 selected from the following group A.
Are substituents. ) Is shown. R ⁵ represents a hydrogen atom or a lower alkyl group, or, together with R ³ ,
Formula - (CH _{2) p} - shows a (wherein, p is showing a 1 to 3.). m represents 1 or 2. n represents 1 or 2. }
A compound represented by or a salt thereof is contained. [Group A] Lower alkyl group, halogeno lower alkyl group, lower alkoxy group, hydroxyl group, alkylenedioxy group having 1 to 4 carbon atoms, acyloxy group, halogen atom, cyano group and nitro group. [Group B] Lower alkylsulfonyl group, lower alkylsulfinyl group and lower alkylthio group.

In the above general formula (I), the "aryl group" of the "optionally substituted aryl group" in the definition of R ⁶ is, for example, phenyl, naphthyl or the like having 5 carbon atoms.
To 12 aromatic hydrocarbon groups, preferably a phenyl group.

"Heteroaryl group" of "optionally substituted heteroaryl group" in the definition of R ⁴ and R ⁶
The term "sulfur atom", "oxygen atom" and / or "nitrogen atom" containing 1 to 3 represents an optionally condensed 5 to 14 membered aromatic heterocyclic group, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, Oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,
Pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,
Indolyl, indazolyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinolinyl, pteridinyl, carbazolyl, carborinyl, phenanthridinyl and acridinyl can be mentioned, and preferably a sulfur atom, an oxygen atom or / and It is an optionally condensed 5 to 10-membered aromatic heterocyclic group containing 1 to 2 nitrogen atoms, and more preferably furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, quinolyl and isoquinolyl groups. is there.

Incidentally, "an optionally substituted heteroary-
In the case where the heteroaryl group includes a nitrogen atom, the substitution position of the “aryl group” may be on the nitrogen atom.

The "lower alkyl group" in the definition of R ³ and R ⁵ and the "lower alkyl group" in the definition of the group A are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl. , T-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, A linear or branched alkyl group having 1 to 6 carbon atoms such as 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, and 2,3-dimethylbutyl is shown, and preferably Is a linear or branched alkyl group having 1 to 4 carbon atoms.

The "lower alkylene group" in the definition of A is, for example, methylene, methylmethylene, ethylene, propylene, trimethylene, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, pentamethylene. Carbon number like hexamethylene
To 6 alkylene groups, preferably methylene, ethylene, trimethylene or tetramethylene.

The "halogeno lower alkyl group" in the definition of Group A means a group in which a halogen atom such as fluorine, chlorine, bromine, iodine is bonded to the above "lower alkyl group", for example, trifluoromethyl, Trichloromethyl,
Difluoromethyl, dichloromethyl, dibromomethyl,
Groups such as fluoromethyl, pentafluoroethyl, 2,2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2-dibromoethyl. Mention may be made of trifluoromethyl, trichloromethyl and pentafluoroethyl.

"Lower alkoxy group" in the definition of group A
The above "lower alkyl group" represents a group bonded to an oxygen atom, for example, methoxy, ethoxy, n-propoxy,
Isopropoxy, n-butoxy, isobutoxy, s-butoxy, t-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-
Methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,
A straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms such as 3-dimethylbutoxy and 2,3-dimethylbutoxy is shown, preferably a straight-chain or branched alkoxy group having 1 to 4 carbon atoms. It is a base.

The "alkylene dioxy group having 1 to 4 carbon atoms" in the definition of group A is a linear or branched alkylene group whose alkylene portion is, for example, methylenedioxy, ethylidenedioxy, It represents a group such as dimethylenedioxy, isopropylenedioxy, trimethylenedioxy, tetramethylenedioxy, and is preferably methylenedioxy.

The "acyloxy group" in the definition of Group A is, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy,
Pentanoyloxy, pivaloyloxy, valeryloxy, isovaleryloxy, octanoyloxy, nonylcarbonyloxy, decylcarbonyloxy, 3-methylnonylcarbonyloxy, 8-methylnonylcarbonyloxy, 3-ethyloctylcarbonyloxy, 3,7- Dimethyloctylcarbonyloxy, undecylcarbonyloxy, dodecylcarbonyloxy, tridecylcarbonyloxy, tetradecylcarbonyloxy, pentadecylcarbonyloxy, hexadecylcarbonyloxy,
1-methylpentadecylcarbonyloxy, 14-methylpentadecylcarbonyloxy, 13,13-dimethyltetradecylcarbonyloxy, heptadecylcarbonyloxy, 15-methylhexadecylcarbonyloxy, octadecylcarbonyloxy, 1-methylheptadecylcarbonyloxy Alkylcarbonyloxy groups such as, nonadecylcarbonyloxy, aicosylcarbonyloxy, henicosylcarbonyloxy, halogenated alkylcarbonyloxy groups such as chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, trifluoroacetyloxy, A lower alkoxyalkylcarbonyloxy group such as methoxyacetyloxy,
(E) Aliphatic acyloxy groups such as unsaturated alkylcarbonyloxy groups such as 2-methyl-2-butenoyloxy; arylcarbonyloxy groups such as benzoyloxy, α-naphthoyloxy, β-naphthoyloxy Halogenated arylcarbonyloxy groups such as 2-bromobenzoyloxy and 4-chlorobenzoyloxy, lower alkylated arylcarbonyloxy such as 2,4,6-trimethylbenzoyloxy and 4-toluoyloxy Groups, lower alkoxylated arylcarbonyloxy groups such as 4-anisoyloxy, 4-nitrobenzoyloxy, nitrated arylcarbonyloxy groups such as 2-nitrobenzoyloxy, 2- (methoxycarbonyl) benzoyl Lower alkoxycarbonylated arylcarbonyloxy groups such as oxy, 4-phenylbenzoyl Aromatic acyloxy groups such as arylated arylcarbonyloxy groups such as xy; lower alkoxycarbonyloxy groups such as methoxycarbonyloxy, ethoxycarbonyloxy, t-butoxycarbonyloxy, isobutoxycarbonyloxy, 2, Alkoxycarbonyloxy groups such as lower alkoxycarbonyloxy groups substituted with halogen or tri-lower alkylsilyl groups such as 2,2-trichloroethoxycarbonyloxy and 2-trimethylsilylethoxycarbonyloxy; vinyloxycarbonyloxy, allyloxycarbonyloxy Alkenyloxycarbonyloxy groups such as; benzyloxycarbonyloxy, 4-methoxybenzyloxycarbonyloxy, 3,4-dimethoxybenzyloxycarbonyloxy, 2-nitrobenzyloxy Carbonyloxy, 4-nitrobenzyloxycarbonyloxy, an aralkyloxycarbonyloxy group in which the aryl ring may be substituted with 1 to 2 lower alkoxy or nitro groups; pivaloyloxymethyloxycarbonyloxy Such as an acyloxy group that is easily hydrolyzed in vivo for the production of a prodrug when administered to a living body; a lower alkanesulfonyloxy group such as methanesulfonyloxy, ethanesulfonyloxy, and 1-propanesulfonyloxy; trifluoromethanesulfonyl Oxy, fluorinated lower alkanesulfonyloxy groups such as pentafluoroethanesulfonyloxy and arylsulfonyloxy groups such as benzenesulfonyloxy, p-toluenesulfonyloxy, and the like, and preferably aliphatic An acyloxy group, more preferably an alkyl carbonyloxy group.

The term "halogen atom" in the definition of group A means fluorine, chlorine, bromine or iodine.

The "lower alkylsulfonyl group" in the definition of Group B is a group in which the above "lower alkyl group" is bonded to a sulfonyl group, and examples thereof include methanesulfonyl, ethanesulfonyl, n-propanesulfonyl, isopropanesulfonyl, n-butanesulfonyl, isobutanesulfonyl, s-butanesulfonyl, t-butanesulfonyl, n-pentanesulfonyl, isopentanesulfonyl, 2-methylbutanesulfonyl, neopentanesulfonyl, n-hexanesulfonyl, 4-methylpentanesulfonyl, 3-methyl Pentanesulfonyl, 2-methylpentanesulfonyl, 3,3-
Dimethylbutanesulfonyl, 2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, 1,2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl, 2,3-
A linear or branched alkanesulfonyl group having 1 to 6 carbon atoms such as dimethylbutanesulfonyl is shown, and a linear or branched alkanesulfonyl group having 1 to 4 carbon atoms is preferable.

The "lower alkylsulfinyl group" in the definition of Group B is a group in which the above "lower alkyl group" is bonded to a sulfinyl group, and examples thereof include methanesulfinyl, ethanesulfinyl, n-propanesulfinyl, isopropanesulfinyl, n-butanesulfinyl, isobutanesulfinyl, s-butanesulfinyl, t-butanesulfinyl, n-pentanesulfinyl, isopentanesulfinyl, 2-methylbutanesulfinyl, neopentanesulfinyl, n-hexanesulfinyl, 4-methylpentanesulfinyl, 3-methyl Pentanesulfinyl, 2-methylpentanesulfinyl, 3,3-dimethylbutanesulfinyl, 2,2-dimethylbutanesulfinyl, 1,
Indicates a linear or branched alkanesulfinyl group having 1 to 6 carbon atoms such as 1-dimethylbutanesulfinyl, 1,2-dimethylbutanesulfinyl, 1,3-dimethylbutanesulfinyl and 2,3-dimethylbutanesulfinyl. It is preferably a straight chain or branched chain alkanesulfinyl group having 1 to 4 carbon atoms.

The "lower alkylthio group" in the definition of group B is a group in which the above "lower alkyl group" is bonded to a sulfur atom, and examples thereof include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio and isobutyl. Thio, s-butylthio, t-butylthio, n-pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, n-hexylthio, 4-methylpentylthio, 3-
Methylpentylthio, 2-methylpentylthio, 3,3-dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, Carbon number 1 like 2,3-dimethylbutylthio
To 6 linear or branched alkylthio groups are shown,
It is preferably a linear or branched alkylthio group having 1 to 4 carbon atoms.

Some of the compounds (I) of the present invention can be converted into salts, and such salts include the following:
Preferably, a hydrohalide such as hydrofluoride, hydrochloride, hydrobromide and hydroiodide, an inorganic acid salt such as nitrate, perchlorate, sulfate and phosphate. ; Lower alkyl sulfonates such as methane sulfonate, trifluoromethane sulfonate, ethane sulfonate, benzene sulfonate, aryl sulfonates such as p-toluene sulfonate, fumarate , Succinate, citrate,
Examples thereof include organic acid salts such as tartrate, oxalate and maleate, and amino acid salts such as glutamate and aspartate.

When R ⁴ represents a "heteroaryl group" containing a nitrogen atom, the nitrogen atom is, for example,
Lower alkylation with a halogeno lower alkyl can give an onium salt, and the corresponding anion of such a salt is preferably a fluorine anion, chlorine anion, bromine anion or iodine anion. Inorganic acid anions such as halogen anion or nitrate anion, perchlorate anion, sulfate anion and phosphate anion can be mentioned.

The compound (I) of the present invention may have an asymmetric carbon in the molecule, and in this case, stereoisomers each having the (R) coordination or the (S) coordination exist. Further, since it has a double bond, there are geometrical isomers of the (Z) form or the (E) form, and each of them or a mixture thereof is included in the present invention.

In the compound (I), preferred compounds include (1) R ¹ and R ² are groups having the formula —R ⁶ (wherein R ⁶
Indicates the same meaning as described above. (2) A compound in which at least one of R ¹ and R ² is an aryl group substituted with a substituent selected from Group A (3) A compound in which R ³ is a hydrogen atom or a lower alkyl group (4) A compound in which R ³ together with R ^{5 represents} the general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3) (5) R ⁴ represents 1 to 5 A compound which is a phenyl group substituted with 4 lower alkoxy groups (6) R ⁴ is an optionally substituted heteroaryl group (the substituents are 1 to 3 substituents selected from the following Group A) A compound (7) X, which is a group), is a compound (8), which is an oxygen atom, (8) R ⁵ represents a hydrogen atom, or, together with R ³ , a compound of the general formula — (CH ₂ ) _p — ( wherein, p is showing a 1 to 3.) the is shown compound (9) m is 1 compound (10) n is 1 compound (11) R ¹ and R ^2, the formula -R ⁶ A group having (in the formula, R ⁶
Indicates the same meaning as described above. ) Or R ¹ and R
^At least one of ² is an aryl group substituted with a substituent selected from Group A, R ³ is a hydrogen atom or a lower alkyl group, and R ⁴ is substituted with 1 to 5 lower alkoxy groups A phenyl group, X is an oxygen atom,
Compounds (12) R ¹ and R ^{2 in} which R ⁵ is a hydrogen atom, m is 1 and n is 1 are groups having the formula —R ⁶ (wherein R ⁶
Indicates the same meaning as described above. ) Or R ¹ and R
^At least one of ² is a substituent selected from Group A,
It is a substituted aryl group in which R ³ together with R ⁵ has the general formula — (CH ₂ ) _p — (wherein p represents 1 to 3).
Wherein R ⁴ is a phenyl group substituted with 1 to 5 lower alkoxy groups, X is an oxygen atom, and m is 1
And the compound (13) R ¹ and R ² in which n is 1 is a group having the formula —R ⁶ (wherein R ⁶
Indicates the same meaning as described above. ) Or R ¹ and R
^At least one of ² is an aryl group substituted with a substituent selected from Group A, R ³ is a hydrogen atom or a lower alkyl group, and R ⁴ is an optionally substituted heteroaryl group ( The substituents are 1 to 3 substituents selected from the following Group A), wherein X is an oxygen atom,
Compounds (14) R ¹ and R ^{2 in} which R ⁵ is a hydrogen atom, m is 1 and n is 1 are groups having the formula —R ⁶ (wherein R ⁶
Indicates the same meaning as described above. ) Or R ¹ and R
^At least one of ² is a substituent selected from Group A,
It is a substituted aryl group in which R ³ together with R ⁵ has the general formula — (CH ₂ ) _p — (wherein p represents 1 to 3).
Wherein R ⁴ is an optionally substituted heteroaryl group (the substituents are 1 to 3 substituents selected from the following group A), X is an oxygen atom, and A compound in which m is 1 and n is 1 (15) A compound in which R ¹ is phenyl substituted with at least one lower alkyl group, halogeno lower alkyl group, lower alkoxy group, halogen atom or cyano group ( 16) A compound in which R ² is a phenyl group, or phenyl substituted with at least one lower alkyl group, halogeno lower alkyl group, lower alkoxy group, cyano group or halogen atom (17) R ² is at least 1 A lower alkyl group, halogeno lower alkyl group, lower alkoxy group or phenyl substituted with halogen atom (18) R ² is at least one lower alkyl group, halogeno lower alkyl A group, a cyano group or a phenyl substituted with a halogen atom (19) In the case of a group having a substituent of R ² , a compound in which the substitution position is the meta position (20) A compound in which R ³ is a hydrogen atom (21) A compound in which R ³ together with R ^{5 represents} a general formula — (CH ₂ ) _p — (in the formula, p represents 1 or 2) (22) R ⁴ represents 1 to 3 A compound (23) R ⁴ which is a phenyl group substituted with one lower alkoxy group is an optionally substituted heteroaryl group (the substituent is one substituent selected from the following Group A). The compound (24) B which is a) is a carbonyl group.

Representative compounds of the present invention include, for example:
The compounds and the geometric isomers thereof shown in Tables 1 to 4 can be mentioned, but the present invention is not limited to these compounds.

In the examples and reference examples in the table, Bu
Is a butyl group, iBu is an isobutyl group, sBu is an s-butyl group, CN is a cyano group, Et is an ethyl group, Np is a naphthyl group, Ph is a phenyl group, Pr is a propyl group, Pyr. Is
A pyridyl group, Quin represents a quinolyl group, and Thi represents a thienyl group.

Table 1

[0031]

[Chemical 5]

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound number R ¹ R ² A ──── ──────────────────────────────── 1 Ph Ph C = O 2 4-CH ₃ OPh 4-CH ₃ OPh C = O 3 4-ClPh 4-ClPh C = O 4 2-Thi 2-Thi C = O 5 4-Pyr 4-Pyr C = O 6 2-Np 2-Np C = O 7 1-Np 1-Np C = O 8 3-Pyr 3-Pyr C = O 9 2-Pyr 2-Pyr C = O 10 2-Quin 2-Quin C = O 11 PhC ≡ C- PhC ≡ C- C = O 12 PhCH = CH- PhCH = CH- C = O 13 3-Thi 3-Thi C = O 14 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh C = O 15 3,4,5-TriCH ₃ OPh 3,4,5- TriCH ₃ OPh C = O 16 Ph 4-CH ₃ OPh C = O 17 Ph 4-ClPh C = O 18 Ph 2-Thi C = O 19 Ph 4-Pyr C = O 20 Ph 2-Np C = O 21 Ph 1-Np C = O 22 Ph 3-Pyr C = O 23 Ph 2-Pyr C = O 24 Ph 2-Quin C = O 25 Ph Ph C≡C- C = O 26 Ph PhCH = CH- C = O 27 Ph 3-Thi C = O 28 Ph 3,4-diCH ₃ OPh C = O 29 Ph 3,4,5-TriCH ₃ OPh C = O 30 4-CH ₃ OPh 4-ClPh C = O 31 4-CH ₃ OPh 2-Thi C = O 32 3-CH ₃ OPh 4-Pyr C = O 33 4-CH ₃ OPh 2-Np C = O 34 4-CH ₃ OPh 1-Np C = O 35 4-CH ₃ OPh 3- Pyr C = O 36 4-CH ₃ OPh 2-Pyr C = O 37 4-CH ₃ OPh 2-Quin C = O 38 4-CH ₃ OPh PhC≡C- C = O 39 4-CH ₃ OPh PhCH = CH -C = O 40 4-CH ₃ OPh 3-Thi C = O 41 4-CH ₃ OPh 3,4-diCH ₃ OPh C = O 42 4-CH ₃ OPh 3,4,5-TriCH ₃ OPh C = O 43 4-ClPh 2-Thi C = O 44 4-ClPh 4-Pyr C = O 45 4-ClPh 2-Np C = O 46 4-ClPh 1-Np C = O 47 2-ClPh 3-Pyr C = O 48 3-ClPh 2-Pyr C = O 49 4-ClPh 2-Quin C = O 50 4-ClPh PhC≡C- C = O 51 4-ClPh PhCH = CH- C = O 52 4-ClPh 3-Thi C = O 53 4-ClPh 3,4-diCH ₃ OPh C = O 54 4-ClPh 3,4,5-TriCH ₃ OPh C = O 55 2-Thi 4-Pyr C = O 56 2-Thi 2-Np C = O 57 2-Thi 1-Np C = O 58 2-Thi 3-Pyr C = O 59 2-Thi 2-Pyr C = O 60 2-Thi 2-Quin C = O 61 2-Thi Ph C≡C- C = O 62 2-Thi PhCH = CH- C = O 63 2-Thi 3-Thi C = O 64 2-Thi 3,4-diCH ₃ OPh C = O 65 2-Thi 3,4,5-TriCH ₃ OPh C = O 66 4-Pyr 2-Np C = O 67 4-Pyr 1-Np C = O 68 4-Pyr 3-Pyr C = O 69 4-Pyr 2-Pyr C = O 70 4-Pyr 2-Quin C = O 71 4-Pyr PhC≡C- C = O 72 4-Pyr PhCH = CH- C = O 73 4-Pyr 3 -Thi C = O 74 4-Pyr 3,4-diCH ₃ OPh C = O 75 4-Pyr 3,4,5-TriCH ₃ OPh C = O 76 2-Np 1-Np C = O 77 2-Np 3 -Pyr C = O 78 2-Np 2-Pyr C = O 79 2-Np 2-Quin C = O 80 2-Np PhC≡C-C = O 81 2-Np PhCH = CH- C = O 82 2- Np 3-Thi C = O 83 2-Np 3,4-diCH ₃ OPh C = O 84 2-Np 3,4,5-TriCH ₃ OPh C = O 85 1-Np 3-Pyr C = O 86 1- Np 2-Pyr C = O 87 1-Np 2-Quin C = O 88 1-Np PhC ≡ C-C = O 89 1-Np PhCH = CH- C = O 90 1-Np 3-Thi C = O 91 1-Np 3,4-diCH ₃ OPh C = O 92 1-Np 3,4,5-TriCH ₃ OPh C = O 93 3-Pyr 2-Pyr C = O 94 3-Pyr 2-Quin C = O 95 3-Pyr PhC≡C- C = O 96 3-Pyr PhCH = CH- C = O 97 3-Pyr 3-Thi C = O 98 3-Pyr 3,4-diCH ₃ OPh C = O 99 3-Pyr 3 , 4,5-TriCH ₃ OPh C = O 100 2-Pyr 2-Quin C = O 101 3-Pyr PhC≡C- C = O 102 2-Pyr PhCH = CH- C = O 103 3-Pyr 3-Thi C = O 104 2-Quin PhC≡C- C = O 105 2-Quin PhCH = CH- C = O 106 2-Quin 3-Thi C = O 107 2-Quin 3,4-diCH ₃ OPh C = O 108 2-Quin 3,4,5-TriCH ₃ OPh C = O 109 PhC ≡ C- PhCH = CH- C = O 110 PhC ≡C- 3-Thi C = O 111 PhC ≡C- 3,4-diCH ₃ OPh C = O 112 PhC ≡C- 3,4,5-TriCH ₃ OPh C = O 113 PhCH = CH- 3-Thi C = O 114 PhCH = CH- 3,4-diCH ₃ OPh C = O 115 PhCH = CH- 3,4,5-TriCH ₃ OPh C = O 116 Ph Ph C = S 117 4-CH ₃ OPh 4-CH ₃ OPh C = S 118 4-ClPh 4-ClPh C = S 119 2-Thi 2-Thi C = S 120 4-F-Ph 4-F-Ph C = S 121 2-Np 2-Np C = S 122 1 -Np 1-Np C = S 123 3-Pyr 3-Pyr C = S 124 2-Pyr 2-Pyr C = S 125 2-Quin 2-Quin C = S 126 PhC ≡ C- PhC ≡ C-C = S 127 PhCH = CH- PhCH = CH- C = S 128 3-Thi 3-Thi C = S 129 Ph 4-CH ₃ OPh C = S 130 Ph 4-ClPh C = S 131 Ph 2-Thi C = S 132 Ph 4-Pyr C = S 133 Ph 2-Np C = S 134 Ph 1-Np C = S 135 Ph 3-Pyr C = S 136 Ph 2-Pyr C = S 137 Ph 2-Quin C = S 138 Ph Ph C≡ C- C = S 139 Ph PhCH = CH- C = S 140 Ph 3-Thi C = S 141 4-CH ₃ OP h 4-ClPh C = S 142 2-CH ₃ OPh 2-Thi C = S 143 3-CH ₃ OPh 4-Pyr C = S 144 4-CH ₃ OPh 2-Np C = S 145 4-CH ₃ OPh 1 -Np C = S 146 4-CH ₃ OPh 3-Pyr C = S 147 4-CH ₃ OPh 2-Pyr C = S 148 4-CH ₃ OPh 2-Quin C = S 149 4-CH ₃ OPh PhC≡C -C = S 150 4-CH ₃ OPh PhCH = CH- C = S 151 4-CH ₃ OPh 3-Thi C = S 152 4-ClPh 2-Thi C = S 153 4-ClPh 4-Pyr C = S 154 3-ClPh 2-Np C = S 155 3-ClPh 1-Np C = S 156 2-ClPh 3-Pyr C = S 157 3-ClPh 2-Pyr C = S 158 4-ClPh 2-Quin C = S 159 4-ClPh PhC ≡ C-C = S 160 4-ClPh PhCH = CH- C = S 161 4-ClPh 3-Thi C = S 162 2-Thi 4-Pyr C = S 163 2-Thi 2-Np C = S 164 2-Thi 1-Np C = S 165 2-Thi 3-Pyr C = S 166 2-Thi 2-Pyr C = S 167 2-Thi 2-Quin C = S 168 2-Thi PhC≡C-C = S 169 2-Thi PhCH = CH- C = S 170 2-Thi 3-Thi C = S 171 4-Pyr 2-Np C = S 172 4-Pyr 1-Np C = S 173 4-Pyr 3-Pyr C = S 174 4-Pyr 2-Pyr C = S 175 4-Pyr 2-Quin C = S 176 4-Pyr PhC≡C- C = S 177 4-Pyr PhCH = CH- C = S 178 4-Pyr 3-Thi C = S 179 2-Np 1-Np C = S 180 2-Np 3-Pyr C = S 181 2-Np 2-Pyr C = S 182 2-Np 2-Quin C = S 183 2-Np PhC ≡ C- C = S 184 2-Np PhCH = CH- C = S 185 2-Np 3-Thi C = S 186 1-Np 3-Pyr C = S 187 1-Np 2-Pyr C = S 188 1-Np 2-Quin C = S 189 1-Np PhC≡C- C = S 190 1-Np PhCH = CH- C = S 191 1-Np 3 -Thi C = S 192 3-Pyr 2-Pyr C = S 193 3-Pyr 2-Quin C = S 194 3-Pyr PhC≡C- C = S 195 3-Pyr PhCH = CH- C = S 196 3- Pyr 3-Thi C = S 197 2-Pyr 2-Quin C = S 198 3-Pyr PhC ≡ C-C = S 199 2-Pyr PhCH = CH- C = S 200 3-Pyr 3-Thi C = S 201 2-Quin PhC≡C- C = S 202 2-Quin PhCH = CH- C = S 203 2-Quin 3-Thi C = S 204 PhC ≡C- PhCH = CH- C = S 205 PhC ≡C- 3- Thi C = S 206 PhCH = CH- 3-Thi C = S 207 Ph Ph SO ₂ 208 4-CH ₃ OPh 4-CH ₃ OPh SO ₂ 209 4-ClPh 4-ClPh SO ₂ 210 2-Thi 2-Thi SO ₂ 211 4-Pyr 4-Pyr SO ₂ 212 2-Np 2-Np SO ₂ 213 1-Np 1-Np SO ₂ 214 3-Pyr 3-Pyr SO ₂ 215 2-Pyr 2-Pyr SO 216 2-Quin 2-Quin SO ₂ 217 PhC ≡ C- PhC ≡ C-SO ₂ 218 PhCH = CH- PhCH = CH -SO ₂ 219 3-Thi 3-Thi SO ₂ 220 Ph 4-CH ₃ OPh SO ₂ 221 Ph 4-ClPh SO ₂ 222 Ph 2-Thi SO ₂ 223 Ph 4-Pyr SO ₂ 224 Ph 2-Np SO ₂ 225 Ph 1-Np SO ₂ 226 Ph 3-Pyr SO ₂ 227 Ph 2-Pyr SO ₂ 228 Ph 2-Quin SO ₂ 229 Ph PhC≡C-SO ₂ 230 Ph PhCH = CH-SO ₂ 231 Ph 3-Thi SO ₂ 232 4-CH ₃ OPh 4-ClPh SO ₂ 233 2-CH ₃ OPh 2-Thi SO ₂ 234 3-CH ₃ OPh 4-Pyr SO ₂ 235 4-CH ₃ OPh 2-Np SO ₂ 236 4-CH ₃ OPh 1-Np SO ₂ 237 4-CH ₃ OPh 3-Pyr SO 238 4-CH ₃ OPh 2-Pyr SO ₂ 239 4-CH ₃ OPh 2-Quin SO ₂ 240 4-CH ₃ OPh PhC≡C-SO ₂ 241 4-CH ₃ OPh PhCH = CH- SO ₂ 242 4-CH ₃ OPh 3-Thi SO ₂ 243 4-ClPh 2-Thi SO ₂ 244 4-ClPh 4-Pyr SO ₂ 245 4-ClPh 2-Np SO ₂ 246 4-ClPh 1-Np SO 247 2-ClPh 3-Pyr SO ₂ 248 3-ClPh 2-Pyr SO ₂ 249 4-ClPh 2-Quin SO ₂ 250 4-ClPh PhC≡C-SO ₂ 251 4-ClPh PhCH = CH-SO ₂ 252 4-ClPh 3-Thi SO ₂ 253 2-Thi 4-Pyr SO ₂ 254 2-Thi 2-Np SO ₂ 255 2-Thi 1-Np SO ₂ 256 2-Thi 3-Pyr SO 257 2-Thi 2-Pyr SO ₂ 258 2-Thi 2-Quin SO ₂ 259 2-Thi PhC≡C -SO ₂ 260 2-Thi PhCH = CH- SO ₂ 261 2-Thi 3-Thi SO ₂ 262 4-Pyr 2-Np SO ₂ 263 4-Pyr 1-Np SO ₂ 264 4-Pyr 3-Pyr SO ₂ 265 4-Pyr 2-Pyr SO ₂ 266 4-Pyr 2-Quin SO ₂ 267 4-Pyr PhC≡C-SO ₂ 268 4-Pyr PhCH = CH-SO 269 4-Pyr 3-Thi SO ₂ 270 2-Np 1 -Np SO ₂ 271 2-Np 3-Pyr SO ₂ 272 2-Np 2-Pyr SO ₂ 273 2-Np 2-Quin SO ₂ 274 2-Np PhC≡C-SO ₂ 275 2-Np PhCH = CH- SO ₂ 276 2-Np 3-Thi SO ₂ 277 1-Np 3-Pyr SO ₂ 278 1-Np 2-Pyr SO ₂ 279 1-Np 2-Quin SO ₂ 280 1-Np PhC≡C-SO ₂ 281 1- Np PhCH = CH- SO 282 1- Np 3-Thi SO 2 283 3-Pyr 2-Pyr SO 2 284 3-Pyr 2-Quin SO 2 28 _{3-Pyr PhC≡C- SO 2 286 3} -Pyr PhCH = CH- SO 2 287 3-Pyr 3-Thi SO 2 288 2-Pyr 2-Quin SO 2 289 3-Pyr PhC≡C- SO 2 290 2- Pyr PhCH = CH- SO ₂ 291 3-Pyr 3-Thi SO ₂ 292 2-Quin PhC ≡ C- SO ₂ 293 2-Quin PhCH = CH- SO ₂ 294 2-Quin 3-Thi SO ₂ 295 PhC ≡ C- PhCH = CH- SO ₂ 296 PhC ≡ C- 3-Thi SO ₂ 297 PhCH = CH- 3-Thi SO ₂ 298 Ph Ph CH ₂ 299 4-CH ₃ OPh 4-CH ₃ OPh CH ₂ 300 4-ClPh 4- ClPh CH ₂ 301 2-Thi 2-Thi CH ₂ 302 4-Pyr 4-Pyr CH ₂ 303 2-Np 2-Np CH ₂ 304 1-Np 1-Np CH ₂ 305 3-Pyr 3-Pyr CH ₂ 306 2 -Pyr 2-Pyr CH ₂ 307 2-Quin 2-Quin CH ₂ 308 PhC ≡ C- PhC ≡ C- CH ₂ 309 PhCH = CH- PhCH = CH- CH ₂ 310 3-Thi 3-Thi CH ₂ 311 3, 4-diCH ₃ OPh 3,4-diCH ₃ OPh CH ₂ 312 3,4,5-TriCH ₃ OPh 3,4,5-TriCH ₃ OPh CH ₂ 313 Ph 4-CH ₃ OPh CH ₂ 314 Ph 4-ClPh CH _{2 315 Ph 2-Thi CH 2} 316 Ph 4-Pyr CH 2 317 Ph 2-Np CH 2 318 Ph 1-Np CH 2 31 _{Ph 3-Pyr CH 2 320 Ph} 2-Pyr CH 2 321 Ph 2-Quin CH 2 322 Ph PhC≡C- CH 2 323 Ph PhCH = CH- CH 2 324 Ph 3-Thi CH 2 325 Ph 3,4-diCH ₃ OPh CH ₂ 326 Ph 3,4,5-TriCH ₃ OPh CH ₂ 327 4-CH ₃ OPh 4-ClPh CH ₂ 328 2-CH ₃ OPh 2-Thi CH ₂ 329 3-CH ₃ OPh 4-Pyr CH ₂ 330 4-CH ₃ OPh 2-Np CH ₂ 331 4-CH ₃ OPh 1-Np CH ₂ 332 4-CH ₃ OPh 3-Pyr CH ₂ 333 4-CH ₃ OPh 2-Pyr CH ₂ 334 4-CH ₃ OPh 2-Quin CH ₂ 335 4-CH ₃ OPh PhC≡C- CH ₂ 336 4-CH ₃ OPh PhCH = CH- CH ₂ 337 4-CH ₃ OPh 3-Thi CH ₂ 338 4-CH ₃ OPh 3,4- diCH ₃ OPh CH ₂ 339 4-CH ₃ OPh 3,4,5-TriCH ₃ OPh CH ₂ 340 4-ClPh 2-Thi CH ₂ 341 4-ClPh 4-Pyr CH ₂ 342 3-ClPh 2-Np CH ₂ 343 3-ClPh 1-Np CH ₂ 344 2-ClPh 3-Pyr CH ₂ 345 3-ClPh 2-Pyr CH ₂ 346 4-ClPh 2-Quin CH ₂ 347 4-ClPh PhC≡C-CH ₂ 348 4-ClPh PhCH = CH- CH ₂ 349 4-ClPh 3-Thi CH ₂ 350 4-ClPh 3,4-diCH ₃ OPh CH ₂ 351 4-ClPh 3,4,5- TriCH ₃ OPh CH ₂ 352 2-Thi 4-Pyr CH ₂ 353 2-Thi 2-Np CH ₂ 354 2-Thi 1-Np CH ₂ 355 2-Thi 3-Pyr CH ₂ 356 2-Thi 2-Pyr CH ₂ 357 2-Thi 2-Quin CH ₂ 358 2-Thi PhC≡C- CH ₂ 359 2-Thi PhCH = CH- CH ₂ 360 2-Thi 3-Thi CH ₂ 361 2-Thi 3,4-diCH ₃ OPh CH ₂ 362 2-Thi 3,4,5-TriCH ₃ OPh CH ₂ 363 4-Pyr 2-Np CH ₂ 364 4-Pyr 1-Np CH ₂ 365 365-Pyr 3-Pyr CH ₂ 366 4-Pyr 2-Pyr CH ₂ 367 4-Pyr 2-Quin CH ₂ 368 4-Pyr PhC≡C- CH ₂ 369 4-Pyr PhCH = CH- CH ₂ 370 4-Pyr 3-Thi CH ₂ 371 4-Pyr 3,4-diCH ₃ OPh CH ₂ 372 4-Pyr 3,4,5-TriCH ₃ OPh CH ₂ 373 2-Np 1-Np CH ₂ 374 2-Np 3-Pyr CH ₂ 375 2-Np 2-Pyr CH ₂ 376 2-Np 2 -Quin CH ₂ 377 2-Np PhC ≡ C- CH ₂ 378 2-Np PhCH = CH- CH ₂ 379 2-Np 3-Thi CH ₂ 380 2-Np 3,4-diCH ₃ OPh CH ₂ 381 2-Np 3,4,5-TriCH ₃ OPh CH ₂ 382 1-Np 3-Pyr CH ₂ 383 1-Np 2-Pyr CH ₂ 384 1-Np 2-Quin CH ₂ 385 1-Np PhC≡C- CH ₂ 386 1-Np PhCH = CH- CH ₂ 387 1-Np 3-Thi CH ₂ 388 1-Np 3,4-diCH ₃ OPh CH ₂ 389 1-Np 3,4,5-TriCH ₃ OPh CH ₂ 390 3-Pyr 2-Pyr CH ₂ 391 3-Pyr 2-Quin CH ₂ 392 3-Pyr PhC ≡ C-CH ₂ 393 3-Pyr PhCH = CH- CH ₂ 394 3-Pyr 3-Thi CH ₂ 395 3-Pyr 3,4-diCH ₃ OPh CH ₂ 396 3-Pyr 3,4,5-TriCH ₃ OPh CH ₂ 397 2-Pyr 2-Quin CH ₂ 398 3-Pyr PhC≡C-CH ₂ 399 2-Pyr PhCH = CH -CH ₂ 400 3-Pyr 3-Thi CH ₂ 401 2-Quin PhC ≡ C- CH ₂ 402 2-Quin PhCH = CH- CH ₂ 403 2-Quin 3-Thi CH ₂ 404 2-Quin 3,4-diCH ₃ OPh CH ₂ 405 2-Quin 3,4,5-TriCH ₃ OPh CH ₂ 406 PhC ≡ C- PhCH = CH- CH ₂ 407 PhC ≡ C- 3-Thi CH ₂ 408 PhC ≡ C- 3,4-diCH ₃ OPh CH ₂ 409 PhC ≡ C- 3,4,5-TriCH ₃ OPh CH ₂ 410 PhCH = CH- 3-Thi CH ₂ 411 3-CH ₃ OPh 3-CH ₃ OPh C = O 412 3-CH ₃ OPh 4-CH ₃ OPh C = O 413 2-CH ₃ OPh 2-CH ₃ OPh C = O 414 2-CH ₃ OPh 3-CH ₃ OPh C = O 415 2-CH ₃ OPh 4-CH ₃ OPh C = O 416 2-ClPh 2-ClPh C = O 417 2-ClPh 3-ClPh C = O 418 2-ClPh 4-ClPh C = O 419 3-ClPh 3-ClPh C = O 420 3-ClPh 4-ClPh C = O 421 2-CH ₃ Ph 2-CH ₃ Ph C = O 422 2-CH ₃ Ph 3-CH ₃ Ph C = O 423 2-CH ₃ Ph 4-CH ₃ Ph C = O 424 3-CH ₃ Ph 3-CH ₃ Ph C = O 425 3-CH ₃ Ph 4-CH ₃ Ph C = O 426 3-CF ₃ Ph 3-CF ₃ Ph C = O 427 3-CF ₃ CH ₂ Ph 3-CF ₃ CH ₂ Ph C = O 428 2-PrOPh 2-PrOPh C = O 429 2-PrOPh 3-PrOPh C = O 430 2-PrOPh 4-PrOPh C = O 431 3-PrOPh 3-PrOPh C = O 432 3-PrOPh 4-PrOPh C = O 433 4-PrOPh 4-PrOPh C = O 434 3-s-BuOPh 3-s-BuOPh C = O 435 4-s-BuOPh 4-s-BuOPh C = O 436 3-i-BuOPh 3-i-BuOPh C = O 437 4-i-BuOPh 4-i-BuOPh C = O 438 2-EtPh 2-EtPh C = O 439 2-EtPh 3-EtPh C = O 440 2-EtPh 4-EtPh C = O 441 3- EtPh 3-EtPh C = O 442 3-EtPh 4-EtPh C = O 443 4-EtPh 4-EtPh C = O 444 2-PrPh 2-PrPh C = O 445 2-PrPh 3-PrPh C = O 446 2- PrPh 4-PrPh C = O 447 3-PrPh 3-PrPh C = O 448 3-PrPh 4-PrPh C = O 449 4-PrPh 4-PrPh C = O 450 3-i-BuPh 3-i-BuPh C = O 451 3-i-BuPh 4-i-BuPh C = O 452 2-ClPh Ph C = O 453 2- ClPh 3-CH ₃ OPh C = O 454 2-ClPh 4-CH ₃ OPh C = O 455 2-ClPh 3-PrOPh C = O 456 2-ClPh 4-PrOPh C = O 457 2-ClPh 3-BuOPh C = O 458 2-ClPh 4-BuOPh C = O 459 2-ClPh 3-CH ₃ Ph C = O 460 2-ClPh 4-CH ₃ Ph C = O 461 2-ClPh 3-CF ₃ Ph C = O 462 2- ClPh 3,4-diCH ₃ OPh C = O 463 2-ClPh 3-CH ₃ O-4-PrOPh C = O 464 2-ClPh 3,4-diPrOPh C = O 465 2-ClPh 3,4-diClPh C = O 466 3-ClPh Ph C = O 467 3-ClPh 3-CH ₃ OPh C = O 468 3-ClPh 4-CH ₃ OPh C = O 469 3-ClPh 4-EtOPh C = O 470 3-ClPh 4-PrOPh C = O 471 3-ClPh 3-i-BuOPh C = O 472 3-ClPh 4-i-BuOPh C = O 473 3-ClPh 2-CH ₃ Ph C = O 474 3-ClPh 3-CH ₃ Ph C = O 475 3-ClPh 4-CH ₃ Ph C = O 476 3-ClPh 3-CF ₃ Ph C = O 477 3-ClPh 3-EtPh C = O 478 3-ClPh 4-EtPh C = O 479 3-ClPh 3 -PrPh C = O 480 3-ClPh 4-PrPh C = O 481 3-ClPh 2,3-diCH ₃ OPh C = O 482 3-ClPh 3,4-diCH ₃ OPh C = O 483 3-ClPh 4-CH ₃ O-3-PrOPh C = O 484 3-ClPh 3,4-diPrOPh C = O 485 3- ClPh 2,3-diClPh C = O 486 3-ClPh 3,4-diClPh C = O 487 4-ClPh 3-CH ₃ OPh C = O 488 4-ClPh 4-CH ₃ OPh C = O 489 4-ClPh 3 -PrOPh C = O 490 4-ClPh 4-PrOPh C = O 491 4-ClPh 3-i-BuOPh C = O 492 4-ClPh 4-i-BuOPh C = O 493 4-ClPh 2,3-diClPh C = O 494 2,3-diClPh Ph C = O 495 2,3-diClPh 3-CH ₃ OPh C = O 496 2,3-diClPh 4-CH ₃ OPh C = O 497 2,3-diClPh 3-PrOPh C = O 498 2,3-diClPh 4-PrOPh C = O 499 2,3-diClPh 3-s-BuOPh C = O 500 2,3-diClPh 4-s-BuOPh C = O 501 2,3-diClPh 3,4 -diCH ₃ OPh C = O 502 2,3-diClPh 3-CH ₃ Ph C = O 503 2,3-diClPh 4-CH ₃ Ph C = O 504 2,3-diClPh 3-EtPh C = O 505 2, 3-diClPh 4-EtPh C = O 506 2,3-diClPh 3-PrPh C = O 507 2,3-diClPh 4-PrPh C = O 508 2,3-diClPh 3-i-BuOPh C = O 509 2, 3-diClPh 4-i-BuOPh C = O 510 3,4-diClPh Ph C = O 511 3,4-diClPh 2-CH ₃ OPh C = O 512 3,4-diClPh 3-CH ₃ OPh C = O 513 3,4-diClPh 4-CH ₃ OPh C = O 514 3,4-diClPh 3-PrOPh C = O 515 3,4-diClPh 4 -PrOPh C = O 516 3,4-diClPh 3-i-BuOPh C = O 517 3,4-diClPh 4-i-BuOPh C = O 518 3,4-diClPh 3-CH ₃ Ph C = O 519 3, 4-diClPh 4-CH ₃ Ph C = O 520 3,4-diClPh 3-PrPh C = O 521 3,4-diClPh 4-PrPh C = O 522 3,4-diClPh 3-i-BuPh C = O 523 3,4-diClPh 4-i-BuPh C = O 524 3-FPh 3-FPh C = O 525 4-FPh 4-FPh C = O 526 3-FPh Ph C = O 527 3-FPh 4-FPh C = O 528 3-FPh 3-CH ₃ OPh C = O 529 3-FPh 4-CH ₃ OPh C = O 530 3-FPh 3-PrOPh C = O 531 3-FPh 4-PrOPh C = O 532 3-FPh 3 -i-BuOPh C = O 533 3-FPh 4-i-BuOPh C = O 534 3-FPh 3-CH ₃ Ph C = O 535 3-FPh 4-CH ₃ Ph C = O 536 3-FPh 3,4 -diCH ₃ Ph C = O 537 3-FPh 3-CF ₃ Ph C = O 538 3-FPh 3-EtPh C = O 539 3-FPh 4-PrPh C = O 540 3-FPh 4-i-BuPh C = O 541 3-FPh 3,4-diCH ₃ OPh C = O 542 3-FPh 2-ClPh C = O 543 3-FPh 3-ClPh C = O 544 3-FPh 4-ClPh C = O 545 3-FPh 2,3-diClPh C = O 546 3-FPh 3,4-diClPh C = O 547 3-FPh 4-PrPh C = O 548 3-FPh 4-i -BuPh C = O 549 4-FPh Ph C = O 550 4-FPh 3,4-diClPh C = O 551 4-FPh 3,4-diCH ₃ OPh C = O 552 4-FPh 3,4,5-triCH ₃ OPh C = O 553 4-FPh 3-CH ₃ Ph C = O 554 4-FPh 4-CH ₃ Ph C = O 555 4-FPh 3,4-diCH ₃ Ph C = O 556 3-CF ₃ Ph Ph C = O 557 3-CF ₃ Ph 3-CH ₃ OPh C = O 558 3-CF ₃ Ph 4-CH ₃ OPh C = O 559 3-CF ₃ Ph 3-PrOPh C = O 560 3-CF ₃ Ph 4 -PrOPh C = O 561 3-CF ₃ Ph 3-i-BuOPh C = O 562 3-CF ₃ Ph 4-i-BuOPh C = O 563 3-CF ₃ Ph 3-CH ₃ Ph C = O 564 3- CF ₃ Ph 4-CH ₃ Ph C = O 565 3-CF ₃ Ph 2,3-diCH ₃ Ph C = O 566 3-CF ₃ Ph 3,4-diCH ₃ Ph C = O 567 3-CF ₃ Ph 3 -EtPh C = O 568 3-CF ₃ Ph 4-EtPh C = O 569 3-CF ₃ Ph 3-PrPh C = O 570 3-CF ₃ Ph 4-PrPh C = O 571 3-CF ₃ Ph 3-i -BuPh C = O 572 3-CF ₃ Ph 4-i-BuPh C = O 573 3-CF ₃ Ph 2,3-diCH ₃ OPh C = O 574 3-CF ₃ Ph 3,4-diCH ₃ OPh C = O 5 75 2-CH ₃ Ph Ph C = O 576 2-CH ₃ Ph 3,4-diCH ₃ Ph C = O 577 2-CH ₃ Ph 3,4-diCH ₃ OPh C = O 578 2-CH ₃ Ph 3- PrPh C = O 579 2-CH ₃ Ph 4-i-BuPh C = O 580 3-CH ₃ Ph Ph C = O 581 3-CH ₃ Ph 1-Np C = O 582 3-CH ₃ Ph 2-Np C = O 583 3-CH ₃ Ph 3,4-diCH ₃ Ph C = O 584 3-CH ₃ Ph 3-EtPh C = O 585 3-CH ₃ Ph 4-EtPh C = O 586 3-CH ₃ Ph 3- PrPh C = O 587 3-CH ₃ Ph 4-PrPh C = O 588 3-CH ₃ Ph 3-i-BuPh C = O 589 3-CH ₃ Ph 4-i-BuPh C = O 590 3-CH ₃ Ph 3,4-diCH ₃ OPh C = O 591 3-CH ₃ Ph 3-CH ₃ OPh C = O 592 3-CH ₃ Ph 4-CH ₃ OPh C = O 593 3-CH ₃ Ph 3-PrOPh C = O 594 3-CH ₃ Ph 4-PrOPh C = O 595 3-CH ₃ Ph 3-i-BuOPh C = O 596 3-CH ₃ Ph 4-i-BuOPh C = O 597 4-CH ₃ Ph Ph C = O 598 4-CH ₃ Ph 3,4-diCH ₃ OPh C = O 599 4-CH ₃ Ph 3-CH ₃ OPh C = O 600 4-CH ₃ Ph 4-CH ₃ OPh C = O 601 4-CH ₃ Ph 3,4-diPrOPh C = O 602 4-CH ₃ Ph 3-CH ₃ O-4-PrOPh C = O 603 3-CH ₃ O-4-PrOPh Ph C = O 604 3-CH ₃ O-4-PrOPh 2-Np C = O 605 3-CH ₃ O-4-PrOPh 1-Np C = O 606 3,4-diPrOPh Ph C = O 607 3-CH ₃ OPh Ph C = O 608 3-PrOPh Ph C = O 609 4-PrOPh Ph C = O 610 3-i-BuOPh Ph C = O 611 4-i-BuOPh Ph C = O 612 3-EtPh Ph C = O 613 3-EtPh 1-Np C = O 614 3-EtPh 2-Np C = O 615 3-PrPh Ph C = O 616 3-PrPh 1-Np C = O 617 3-PrPh 2-Np C = O 618 3-i-BuPh Ph C = O 619 3-i-BuPh 1-Np C = O 620 3-i-BuPh 2-Np C = O 621 3,4-diCH ₃ Ph Ph C = O 622 Ph 3-CH ₃ O-4-EtO-Ph C = O 623 Ph 3-CH ₃ O-4 -EtO-Ph C = S 624 Ph 3-CH ₃ O-4-EtO-Ph CH ₂ 625 Ph 3-CH ₃ O-4-PrO-Ph C = S 626 Ph 3-CH ₃ O-4-PrO- Ph CH ₂ 627 Ph 3-CH ₃ O-4-BuO-Ph C = O 628 Ph 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 629 Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 630 Ph 3-EtO-4-CH ₃ O-Ph C = O 631 Ph 3-PrO-4-CH ₃ O-Ph C = O 632 Ph 3-BuO-4-CH ₃ O-Ph C = O 633 Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 634 Ph 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 635 Ph 3 , 4-di-CH ₃ O-Ph C = S 636 Ph 3,4- di-CH ₃ O-Ph CH ₂ 637 Ph 3,4-di-EtO-Ph C = O 638 Ph 3,4-di-PrO-Ph C = S 638 Ph 3,4-di-PrO-Ph CH ₂ 640 Ph 3,4-di-BuO-Ph C = O 641 Ph 4-EtOPh C = O 642 Ph 4-BuOPh C = O 643 Ph 4-C ₅ H ₁₁ OPh C = O 644 Ph 4-C ₆ H ₁₃ OPh C = O 645 Ph 3-CH ₃ OPh C = O 646 Ph 3-EtOPh C = O 647 Ph 3-BuOPh C = O 648 Ph 3-BuPh C = O 649 Ph 4-BuPh C = O 650 Ph 3- C ₅ H ₁₁ OPh C = O 651 Ph 3-C ₆ H ₁₃ OPh C = O 652 Ph 3,4-diEtPh C = O 653 Ph 3,4-diPrPh C = O 654 Ph 3,4-diBuPh C = O 655 3-BuOPh 3-BuOPh C = O 656 4-ClPh 2,3-di-CH ₃ O-Ph C = O 657 2,3-diClPh 3-BuPh C = O 658 2,3-diClPh 4-BuPh C = O 659 3,4-diClPh 3-EtPh C = O 660 3,4-diClPh 4-EtPh C = O 661 3,4-diClPh 3-BuPh C = O 662 3,4-diClPh 4-BuPh C = O 663 3,4-diClPh 4-CH ₃ OPh C = S 664 3,4-diClPh 4-CH ₃ OPh CH ₂ 665 3,4-diClPh 4-PrOPh C = S 666 3,4-diClPh 3-PrOPh CH ₂ 667 3,4-diClPh 3-BuOPh C = O 668 3,4-diClPh 4-BuOPh C = O 6 69 3,4-diClPh 3,4-di-CH ₃ O-Ph C = O 670 3-CF ₃ Ph 3-EtOPh C = O 671 3-CF ₃ Ph 4-EtOPh C = O 672 3-CF ₃ Ph 3-BuOPh C = O 673 3-CF ₃ Ph 3-C ₅ H ₁₁ OPh C = O 674 3-CF ₃ Ph 3-C ₆ H ₁₃ OPh C = O 675 3-CF ₃ Ph 4-BuOPh C = O 676 3-CF ₃ Ph 4-C ₅ H ₁₁ OPh C = O 677 3-CF ₃ Ph 4-C ₆ H ₁₃ OPh C = O 678 3-CF ₃ Ph 4-BuPh C = O 679 3-CF ₃ Ph 3-EtO-4-CH ₃ O-Ph C = O 680 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph C = O 681 3-CF ₃ Ph 3-BuO-4-CH ₃ O- Ph C = O 682 3-CF ₃ Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 683 3-CF ₃ Ph 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 684 3-CF ₃ Ph 3-CH ₃ O-4-EtO-Ph C = O 685 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph C = O 686 3-CF ₃ Ph 3- CH ₃ O-4-PrO-Ph C = S 687 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph CH ₂ 688 3-CF ₃ Ph 3-CH ₃ O-4-BuO-Ph C = O 689 3-CF ₃ Ph 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 690 3-CF ₃ Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 691 3-CF ₃ Ph 3,4-di-CH ₃ O-Ph C = S 692 3-CF ₃ Ph 3,4-di-CH ₃ O-Ph CH ₂ 693 3-CF ₃ Ph 3,4-di- EtO -Ph C = O 694 3-CF ₃ Ph 3,4-di-PrO-Ph C = O 695 3-CF ₃ Ph 3,4-di-PrO-Ph C = S 696 3-CF ₃ Ph 3,4 -di-PrO-Ph CH ₂ 697 3-CF ₃ Ph 3,4-di-BuO-Ph C = O 698 3-CH ₃ Ph 3-CH ₃ Ph C = S 699 3-CH ₃ Ph 3-CH ₃ Ph CH ₂ 700 3-CH ₃ Ph 3-BuPh C = O 701 3-CH ₃ Ph 4-BuPh C = O 702 3-CH ₃ Ph 3-EtOPh C = O 703 3-CH ₃ Ph 4-EtOPh C = O 704 3-CH ₃ Ph 3-BuOPh C = O 705 3-CH ₃ Ph 3-C ₅ H ₁₁ OPh C = O 706 3-CH ₃ Ph 3-C ₆ H ₁₃ OPh C = O 707 3-CH ₃ Ph 4-BuOPh C = O 708 3-CH ₃ Ph 4-C ₅ H ₁₁ OPh C = O 709 3-CH ₃ Ph 4-C ₆ H ₁₃ OPh C = O 710 3-CH ₃ Ph 3-CH ₃ O -4-PrO-Ph C = O 711 3-CH ₃ Ph 3-CH ₃ O-4-PrO-Ph C = S 712 3-CH ₃ Ph 3-CH ₃ O-4-PrO-Ph CH ₂ 713 3 -CH ₃ Ph 3-CH ₃ O-4-EtO-Ph C = O 714 3-CH ₃ Ph 3-CH ₃ O-4-BuO-Ph C = O 715 3-CH ₃ Ph 3-CH ₃ O- 4-C ₅ H ₁₁ O-Ph C = O 716 3-CH ₃ Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 717 3-CH ₃ Ph 3-EtO-4-CH ₃ O-Ph C = O 718 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph C = O 719 3-CH ₃ Ph 3-BuO-4-CH ₃ O-Ph C = O 720 3-CH ₃ Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 721 3-CH ₃ Ph 3-C ₆ H ₁₃ O-4-CH ₃ O -Ph C = O 722 3-CH ₃ Ph 3,4-di-CH ₃ O-Ph C = S 723 3-CH ₃ Ph 3,4-di-CH ₃ O-Ph CH ₂ 724 3-CH ₃ Ph 3,4-di-EtO-Ph C = O 725 3-CH ₃ Ph 3,4-di-PrO-Ph C = O 726 3-CH ₃ Ph 3,4-di-BuO-Ph C = O 727 3 , 4-Methylenedioxy-Ph Ph C = O 728 3,4-Methylenedioxy-Ph 3-ClPh C = O 729 3,4-Methylenedioxy-Ph 3,4-diClPh C = O 730 3,4 -Methylenedioxy-Ph 3-CH ₃ Ph C = O 731 3,4-Methylenedioxy-Ph 3-CF ₃ Ph C = O 732 3-ClPh 3-EtOPh C = O 733 3-ClPh 4-EtOPh C = O 734 3-ClPh 3-BuOPh C = O 735 3-ClPh 3-C ₅ H ₁₁ OPh C = O 736 3-ClPh 3-C ₆ H ₁₃ OPh C = O 737 3-ClPh 4-BuOPh C = O 738 3-ClPh 4-C ₅ H ₁₁ OPh C = O 739 3-ClPh 4-C ₆ H ₁₃ OPh C = O 740 3-ClPh 3-CH ₃ O-4-PrO-Ph C = O 741 3-ClPh 3-CH ₃ O-4-PrO-Ph C = S 742 3-ClPh 3-CH ₃ O-4-PrO-Ph CH ₂ 743 3-ClPh 3-CH ₃ O-4-EtO-Ph C = O 74 4 3-ClPh 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 745 3-ClPh 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 746 3-ClPh 3- EtO-4-CH ₃ O-Ph C = O 747 3-ClPh 3-BuO-4-CH ₃ O-Ph C = O 748 3-ClPh 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 749 3-ClPh 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 750 3-ClPh 3,4-di-CH ₃ O-Ph C = S 751 3-ClPh 3,4- di-CH ₃ O-Ph CH ₂ 752 3-ClPh 3,4-di-EtO-Ph C = O 753 3-ClPh 3,4-di-PrO-Ph C = S 754 3-ClPh 3,4-di -PrO-Ph CH ₂ 755 3-ClPh 3,4-di-BuO-Ph C = O 756 3-ClPh 3-BuPh C = O 757 3-ClPh 4-BuPh C = O 758 1-Np 3-ClPh C = O 759 2-Np 3-ClPh C = O 760 1-Np 3,4-diClPh C = O 761 2-Np 3,4-diClPh C = O 762 1-Np 3-CF ₃ Ph C = O 763 2 -Np 3-CF ₃ Ph C = O 764 3-BrPh 3-BrPh C = O 765 3-BrPh 3-CH ₃ OPh C = O 766 3-BrPh 3-EtOPh C = O 767 3-BrPh 3-PrOPh C = O 768 3-BrPh 3-BuOPh C = O 769 3-BrPh 3-C ₅ H ₁₁ OPh C = O 770 3-BrPh 3-C ₆ H ₁₃ OPh C = O 771 3-BrPh 4-CH ₃ OPh C = O 772 3-BrPh 4-EtOPh C = O 772 3-BrPh 4-PrOPh C = O 774 3-BrPh 4-BuOPh C = O 775 3-BrPh 4-C ₅ H ₁₁ OPh C = O 776 3-BrPh 4-C ₆ H ₁₃ OPh C = O 777 3-BrPh 3-CH ₃ O- 4-EtO-Ph C = O 778 3-BrPh 3-CH ₃ O-4-PrO-Ph C = O 779 3-BrPh 3-CH ₃ O-4-BuO-Ph C = O 780 3-BrPh 3- EtO-4-CH ₃ O-Ph C = O 781 3-BrPh 3-PrO-4-CH ₃ O-Ph C = O 782 3-BrPh 3-BuO-4-CH ₃ O-Ph C = O 783 3 -BrPh 3,4-di-EtO-Ph C = O 784 3-BrPh 3,4-di-PrO-Ph C = O 785 3-BrPh 3-CH ₃ Ph C = O 786 3-BrPh 3-Et- Ph C = O 787 3-BrPh 4-CH ₃ Ph C = O 788 3-BrPh 4-EtPh C = O 789 3-BrPh 1-Np C = O 790 3-BrPh 2-Np C = O 791 3,5 -diClPh 3-CH ₃ OPh C = O 792 3,5-diClPh 3-PrOPh C = O 793 3,5-diClPh 4-CH ₃ OPh C = O 794 3,5-diClPh 4-PrOPh C = O 795 3 , 5-diClPh 3-EtPh C = O 796 3,5-diClPh 4-EtPh C = O 797 3,5-diClPh 3-PrPh C = O 798 3,5-diClPh 4-PrPh C = O 799 3,5 -diClPh 4-EtOPh C = O 800 3,5-diClPh 3,4-diCH ₃ O-Ph C = O 801 2,3-diClPh 4-EtOPh C = O 802 2,5-diClPh 3-CH ₃ OPh C = O 803 2, 5-diClPh 4-CH ₃ OPh C = O 804 2,5-diClPh 3-EtOPh C = O 805 2,5-diClPh 4-EtOPh C = O 806 2,5-diClPh 3-PrOPh C = O 807 2, 5-diClPh 4-PrOPh C = O 808 2,5-diClPh 4-CH ₃ Ph C = O 809 2,5-diClPh 4-EtPh C = O 810 2,5-diClPh 4-PrPh C = O 811 2, 5-diClPh 3,4-diCH ₃ O-Ph C = O 812 2,6-diClPh 3-CH ₃ OPh C = O 813 2,6-diClPh 4-CH ₃ OPh C = O 814 2,6-diClPh 3 -EtOPh C = O 815 2,6-diClPh 4-EtOPh C = O 816 2,6-diClPh 3-PrOPh C = O 817 2,6-diClPh 4-PrOPh C = O 818 2,6-diClPh 3,4 -diCH ₃ O-Ph C = O 819 2,6-diClPh 4-CH ₃ Ph C = O 820 2,6-diClPh 4-EtPh C = O 821 2,6-diClPh 4-PrPh C = O 822 2, 4-diClPh 3-CH ₃ OPh C = O 823 2,4-diClPh 4-CH ₃ OPh C = O 824 2,4-diClPh 3-EtOPh C = O 825 2,4-diClPh 4-EtOPh C = O 826 2,4-diClPh 3-PrOPh C = O 827 2,4-diClPh 4-PrOPh C = O 828 2,4-diClPh 3,4-diCH ₃ O-Ph C = O 829 2,4-diClPh 4-CH ₃ Ph C = O 830 2,4-diClPh 4-EtPh C = O 831 2,4-diClPh 4-PrPh C = O 832 3,5-di CH ₃ Ph 4-CH ₃ OPh C = O 833 3,5-diCH ₃ Ph 4-EtOPh C = O 834 3,5-diCH ₃ Ph 4-PrOPh C = O 835 3,5-diCH ₃ Ph 3,4 -diCH ₃ O-Ph C = O 836 3,5-diCH ₃ Ph 4-CH ₃ Ph C = O 837 3,5-diCH ₃ Ph 4-EtPh C = O 838 3,5-diCH ₃ Ph 4-PrPh C = O 839 3,5-diCH ₃ Ph 3-ClPh C = O 840 3,5-diCH ₃ Ph 4-ClPh C = O 841 3,5-diCH ₃ Ph 3-FPh C = O 842 3,5- diCH ₃ Ph 4-FPh C = O 843 3,5-diCH ₃ Ph 3-BrPh C = O 844 3,5-diCH ₃ Ph 4-BrPh C = O 845 3,5-diCF ₃ Ph 4-CH ₃ OPh C = O 846 3,5-diCF ₃ Ph 4-EtOPh C = O 847 3,5-diCF ₃ Ph 4-PrOPh C = O 848 3,5-diCF ₃ Ph 3,4-diCH ₃ O-Ph C = O 849 3,5-diCF ₃ Ph 4-CH ₃ Ph C = O 850 3,5-diCF ₃ Ph 4-EtPh C = O 851 3,5-diCF ₃ Ph 4-PrPh C = O 852 3,5- diCF ₃ Ph 3-ClPh C = O 853 3,5-diCF ₃ Ph 4-ClPh C = O 854 3,5-diCF ₃ Ph 3-FPh C = O 855 3,5-diCF ₃ Ph 4-FPh C = O 856 3,5-diCF ₃ Ph 3-BrPh C = O 857 3,5-diCF ₃ Ph 4-BrPh C = O 858 3,5-diFPh 4-CH ₃ OPh C = O 859 3,5-diFPh 4 -EtOPh C = O 86 3,5-diFPh 4-PrOPh C = O 861 3,5-diFPh 4-CH 3 Ph C = O 862 3,5-diFPh 4-EtPh C = O 863 3,5-diFPh 4-PrPh C = O 864 3,5-diFPh 3-ClPh C = O 865 3,5-diFPh 4-ClPh C = O 866 3-Cl-5-F-Ph 4-CH ₃ OPh C = O 867 3-Cl-5-F- Ph 4-EtOPh C = O 868 3-Cl-5-F-Ph 4-EtPh C = O 869 3-Cl-5-F-Ph 4-PrPh C = O 870 3,5-diBrPh 4-CH ₃ OPh C = O 871 3-FPh 4-EtPh C = O 872 3-FPh 4-EtOPh C = O 873 3-CN-Ph 4-CH ₃ OPh C = O 874 3-CN-Ph 4-EtOPh C = O 875 3-CN-Ph 4-EtPh C = O 876 3-CN-Ph 4-PrPh C = O 877 3-Cl-5-CH ₃ Ph 4-CH ₃ OPh C = O 878 3-Cl-5-CH ₃ Ph 4-EtOPh C = O 879 3-Cl-5-CH ₃ Ph 4-EtPh C = O 880 3-Cl-5-CH ₃ Ph 4-PrPh C = O ─────────── ───────────────────────── Table 2

[0033]

[Chemical 6]

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound number R ¹ R ² R ⁴ ─── ───────────────────────────────── 2 -1 3-ClPh 3-ClPh 3,4-diCH ₃ OPh 2 -2 4-ClPh 4-ClPh 3,4-diCH ₃ OPh 2 -3 3-ClPh 2,3-diClPh 3,4-diCH ₃ OPh 2 -4 3-ClPh 3,4-diClPh 3,4-diCH ₃ OPh 2 -5 4-ClPh 2,3-diClPh 3,4-diCH ₃ OPh 2 -6 3-ClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2 -7 3-ClPh 4-CH ₃ OPh 3, 4-diCH ₃ OPh 2 -8 3-ClPh 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2 -9 3-ClPh 3-CH ₃ O-3-PrOPh 3,4-diCH ₃ OPh 2-10 2,3-diClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-11 2,3-diClPh 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-12 2,3-diClPh 3-CH ₃ Ph 3,4-diCH ₃ OPh 2-13 2,3-diClPh 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-14 3,4-diClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-15 3,4-diClPh 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-16 3,4-diClPh 4-PrOPh 3,4-diCH ₃ OPh 2-17 3,4-diClPh 4-i-BuOPh 3, 4-diCH ₃ OPh 2-18 3,4-diClPh 3-C H ₃ Ph 3,4-diCH ₃ OPh 2-19 3,4-diClPh 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-20 3,4-diClPh 4-i-BuPh 3,4-diCH ₃ OPh 2-21 3-CH ₃ Ph 3-CH ₃ Ph 3,4-diCH ₃ OPh 2-22 3-CH ₃ Ph 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-23 3-CH ₃ Ph 4- CH ₃ OPh 3,4-diCH ₃ OPh 2-24 3-CH ₃ Ph 3-PrOPh 3,4-diCH ₃ OPh 2-25 3-CH ₃ Ph 4-PrOPh 3,4-diCH ₃ OPh 2-26 3 -CH ₃ Ph 3-i-BuOPh 3,4-diCH ₃ OPh 2-27 3-CH ₃ Ph 4-i-BuOPh 3,4-diCH ₃ OPh 2-28 3-CH ₃ Ph 3,4-diCH ₃ Ph 3,4-diCH ₃ OPh 2-29 3-CH ₃ Ph 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2-30 3-CH ₃ Ph 3,4-diPrOPh 3,4-diCH ₃ OPh 2-31 3-CH ₃ Ph 3-CH ₃ O-4-PrOPh 3,4-diCH ₃ OPh 2-32 3-CF ₃ Ph 3-ClPh 3,4-diCH ₃ OPh 2-33 3-CF ₃ Ph 4-ClPh 3,4-diCH ₃ OPh 2-34 3-CF ₃ Ph 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-35 3-CF ₃ Ph 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-36 3-CF ₃ Ph 3-PrOPh 3,4-diCH ₃ OPh 2-37 3-CF ₃ Ph 4-PrOPh 3,4-diCH ₃ OPh 2-38 3-CF ₃ Ph 3-i-BuOPh 3 , 4-diCH ₃ OPh 2-39 3-CF ₃ Ph 4-i-BuOPh 3,4-diCH ₃ OPh 2-40 3-CF ₃ Ph 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2-- 41 3-ClPh 3-ClPh 3-CH ₃ OPh 2-42 3- ClPh 4-ClPh 3-CH ₃ OPh 2-43 3-ClPh 3-CH ₃ OPh 3-CH ₃ OPh 2-44 3-ClPh 4-CH ₃ OPh 3-CH ₃ OPh 2-45 3-ClPh 3,4 -diCH ₃ OPh 3-CH ₃ OPh 2-46 3,4-diClPh 4-CH ₃ OPh 3-CH ₃ OPh 2-47 3,4-diClPh 4-PrOPh 3-CH ₃ OPh 2-48 3,4- diClPh 4-i-BuOPh 3-CH ₃ OPh 2-49 3-CH ₃ Ph 3-CH ₃ Ph 3-CH ₃ OPh 2-50 3-CH ₃ Ph 4-CH ₃ OPh 3-CH ₃ OPh 2-51 3-CH ₃ Ph 4-PrOPh 3-CH ₃ OPh 2-52 3-CH ₃ Ph 4-i-BuOPh 3-CH ₃ OPh 2-53 3-CH ₃ Ph 3,4-diCH ₃ OPh 3-CH ₃ OPh 2-54 3-CH ₃ Ph 3,4-diClPh 3-CH ₃ OPh 2-55 3-CH ₃ Ph 3,4-diCH ₃ Ph 3-CH ₃ OPh 2-56 3-CF ₃ Ph 4-CH ₃ OPh 3-CH ₃ OPh 2-57 3-CF ₃ Ph 4-PrOPh 3-CH ₃ OPh 2-58 3-CF ₃ Ph 4-i-BuOPh 3-CH ₃ OPh 2-59 3-CF ₃ Ph 3 , 4-diCH ₃ OPh 3-CH ₃ OPh 2-60 3-CF ₃ Ph 3,4-diClPh 3-CH ₃ OPh 2-61 3-CF ₃ Ph 3,4-diCH ₃ Ph 3-CH ₃ OPh 2 -62 3-ClPh 3-ClPh 4-CH ₃ OPh 2-63 3-ClPh 4-ClPh 4-CH ₃ OPh 2-64 3-ClPh 3-CH ₃ OPh 4-CH ₃ OPh 2-65 3-ClPh 4 -CH ₃ OPh 4-CH ₃ OPh 2-66 3-ClPh 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-67 3,4-diClPh 4-CH ₃ OPh 4-CH ₃ OPh 2-68 3, 4-diClPh 4-P rOPh 4-CH ₃ OPh 2-69 3,4-diClPh 4-i-BuOPh 4-CH ₃ OPh 2-70 3-CH ₃ Ph 3-CH ₃ Ph 4-CH ₃ OPh 2-71 3-CH ₃ Ph 4-CH ₃ OPh 4-CH ₃ OPh 2-72 3-CH ₃ Ph 4-PrOPh 4-CH ₃ OPh 2-73 3-CH ₃ Ph 4-i-BuOPh 4-CH ₃ OPh 2-74 3-CH ₃ Ph 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-75 3-CH ₃ Ph 3,4-diClPh 4-CH ₃ OPh 2-76 3-CH ₃ Ph 3,4-diCH ₃ Ph 4-CH ₃ OPh 2-77 3-CF ₃ Ph 4-CH ₃ OPh 4-CH ₃ OPh 2-78 3-CF ₃ Ph 4-PrOPh 4-CH ₃ OPh 2-79 3-CF ₃ Ph 4-i-BuOPh 4 -CH ₃ OPh 2-80 3-CF ₃ Ph 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-81 3-CF ₃ Ph 3,4-diClPh 4-CH ₃ OPh 2-82 3-CF ₃ Ph 3,4-diCH ₃ Ph 4-CH ₃ OPh 2-83 Ph 3,4-di-CH ₃ O-Ph 3,4-di-CH ₃ O-Ph 2-84 Ph 3,4-di-CH ₃ O-Ph 3-CH ₃ O-Ph 2-85 Ph 3,4-di-CH ₃ O-Ph 4-CH ₃ O-Ph 2-86 Ph 3,4-di-PrO-Ph 3,4-di -CH ₃ O-Ph 2-87 Ph 3,4-di-PrO-Ph 3-CH ₃ O-Ph 2-88 Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-89 Ph 3-CH ₃ O-4-PrO-Ph 3,4-di-CH ₃ O-Ph 2-90 Ph 3-CH ₃ O-4-PrO-Ph 3-CH ₃ O-Ph 2-91 Ph 3- CH ₃ O-4-PrO-Ph 4-CH ₃ O-Ph 2-92 3-Cl-Ph 3,4-di-PrO-Ph 3,4-di-CH ₃ O-Ph 2-93 3-Cl -Ph 3,4-di-PrO-P h 3-CH ₃ O-Ph 2-94 3-Cl-Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-95 3-Cl-Ph 3-PrO-4-CH ₃ O- Ph 3,4-di-CH ₃ O-Ph 2-96 3-Cl-Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2-97 3-Cl-Ph 3-PrO- 4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-98 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 3,4-di-CH ₃ O-Ph 2-99 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2-100 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-101 3 -CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 3,4-di-CH ₃ O-Ph 2-102 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 3-CH ₃ O -Ph 2-103 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 4-CH ₃ O-Ph 2-104 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 3,4 -di-CH ₃ O-Ph 2 -105 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2 -106 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-107 3-CF ₃ Ph 3,4-di-PrO-Ph 3,4-di-CH ₃ O-Ph 2-108 3-CF ₃ Ph 3,4- di-PrO-Ph 3-CH ₃ O-Ph 2-109 3-CF ₃ Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-110 3,4-diCH ₃ OPh Ph 3,5 -diCH ₃ O-4-PrSPh 2-111 3,4-diCH ₃ OPh Ph 4-CH ₃ SPh 2-112 3-CH ₃ O-4-PrOPh Ph 3-CH ₃ S-4,5-diCH ₃ OPh 2-113 3-CH ₃ O-4-PrOPh 3-CH ₃ Ph 3,4,5-triCH ₃ Ph 2-114 3-CH ₃ O-4-PrOPh 3-CH ₃ Ph 3,4,5-triEtPh 2-115 3-CH ₃ O-4-PrOPh 3-ClPh 3,4-diEtPh 2-116 3-CH ₃ O-4-PrOPh 3-CF ₃ Ph 4-EtPh 2-117 4-PrOPh 3,4-diClPh 4-ClPh 2-118 4-PrOPh 3-CH ₃ Ph 3,4-diClPh 2-119 3-PrOPh 3-CF ₃ Ph 3-ClPh 2-120 3-ClPh 3-ClPh 3-Cl-4-CH ₃ Ph 2-121 3-CH ₃ Ph 3-CH ₃ Ph 3-CH ₃ -4-ClPh 2-122 3-CH ₃ Ph 3-CH ₃ Ph Ph 2-123 3-CH ₃ OPh Ph 2-CF ₃ Ph 2-124 3-EtOPh Ph 3-CF ₃ Ph 2-125 4-CH ₃ OPh Ph 4-CF ₃ Ph 2-126 4-EtOPh Ph 3,4,5-triCF ₃ Ph 2-127 3,4-diCH ₃ OPh Ph 2-CF ₃ Ph 2-128 3,4-diEtOPh Ph 3-CF ₃ Ph 2-129 3-CH ₃ OPh 4-ClPh 4-CF ₃ Ph 2-130 3 -EtOPh 4-BrPh 3,4,5-triCF ₃ Ph 2-131 4-CH ₃ OPh 4-FPh 2-CF ₃ Ph 2-132 4-EtOPh 4-ClPh 3-CF ₃ Ph 2-133 3,4 -diCH ₃ OPh 4-FPh 4-CF ₃ Ph 2-134 3,4-diEtOPh 4-BrPh 3,4,5-triCF ₃ Ph 2-135 3-CH ₃ OPh 4-CH ₃ Ph 2-CF ₃ Ph 2-136 3-EtOPh 4-CH ₃ Ph 3-CF ₃ Ph 2-137 4-CH ₃ OPh 4-CH ₃ Ph 4-CF ₃ Ph 2-138 4-EtOPh 4-CH ₃ Ph 3,4,5 -triCF ₃ Ph 2-139 3,4-diCH ₃ OPh 4-CH ₃ Ph 2-CF ₃ Ph 2-140 3,4-diEtOPh 4-CH ₃ Ph 3-CF ₃ Ph 2-141 3-CH ₃ OPh Four- CF ₃ Ph 4-CF ₃ Ph 2-142 3-EtOPh 4-CF ₃ Ph 3,4,5-triCF ₃ Ph 2-143 4-CH ₃ OPh 4-CF ₃ Ph 2-CF ₃ Ph 2-144 4 -EtOPh 4-CF ₃ Ph 3-CF ₃ Ph 2-145 3,4-diCH ₃ OPh 4-CF ₃ Ph 4-CF ₃ Ph 2-146 3,4-diEtOPh 4-CF ₃ Ph 3,4,5 -triCF ₃ Ph 2-147 ₃ -CH ₃ OPh 3,4-diClPh 2-CF ₃ Ph 2-148 3-EtOPh 3,4-diFPh 3-CF ₃ Ph 2-149 4-CH ₃ OPh 3,4- diFPh 4-CF ₃ Ph 2-150 4-EtOPh 3,4-diClPh 3,4,5-triCF ₃ Ph 2-151 3,4-diCH ₃ OPh 3,4-diClPh 2-CF ₃ Ph 2-152 3 , 4-diEtOPh 3,4-diFPh 3-CF ₃ Ph 2-153 3-CH ₃ OPh Ph 2-EtOPh 2-154 3-EtOPh Ph 3-EtOPh 2-155 4-CH ₃ OPh Ph 4-EtOPh 2-- 156 4-EtOPh Ph 2,3,4-triEtOPh 2-157 3,4-diCH ₃ OPh Ph 2-OHPh 2-158 3,4-diEtOPh Ph 3-OHPh 2-159 3-CH ₃ OPh 4-ClPh 4 -OHPh 2-160 3-EtOPh 4-BrPh 3,4,5-triOHPh 2-161 4-CH ₃ OPh 4-FPh 2-CH ₃ SPh 2-162 4-EtOPh 4-ClPh 3-CH ₃ SPh 2-- 163 3,4-diCH ₃ OPh 4-FPh 4-CH ₃ SPh 2-164 3,4-diEtOPh 4-BrPh 3,4,5-triCH ₃ SPh 2-165 3-CH ₃ OPh 4-CH ₃ Ph 3 , 4,5-triEtSPh 2-166 3-EtOPh 4-CH ₃ Ph 2-EtOPh 2-167 4-CH ₃ OPh 4-CH ₃ Ph 3-EtOPh 2-168 4-EtOPh 4-CH ₃ Ph 4-EtOPh 2-169 3,4-diCH ₃ OPh 4-CH ₃ Ph 2,3,4-triEtOPh 2-170 3,4-diEtOPh 4-CH ₃ Ph 2-OHPh 2 -171 3-CH ₃ OPh 4-CF ₃ Ph 3-OHPh 2-172 3-EtOPh 4-CF ₃ Ph 4-OHPh 2-173 4-CH ₃ OPh 4-CF ₃ Ph 3,4,5-triOHPh 2 -174 4-EtOPh 4-CF ₃ Ph 2-CH ₃ SPh 2-175 3,4-diCH ₃ OPh 4-CF ₃ Ph 3-CH ₃ SPh 2-176 3,4-diEtOPh 4-CF ₃ Ph 4- CH ₃ SPh 2-177 3-CH ₃ OPh 3,4-diClPh 3,4,5-triCH ₃ SPh 2-178 3-EtOPh 3,4-diFPh 3,4,5-triEtSPh 2-179 4-CH ₃ OPh 3,4-diFPh 2-EtOPh 2-180 4-EtOPh 3,4-diClPh 3-EtOPh 2-181 3,4-diCH ₃ OPh 3,4-diClPh 4-EtOPh 2-182 3,4-diEtOPh 3 , 4-diFPh 2,3,4-triEtOPh 2-183 3-CH ₃ OPh Ph 2-ClPh 2-184 3-EtOPh Ph 3-ClPh 2-185 4-CH ₃ OPh Ph 4-ClPh 2-186 4- EtOPh Ph 3,4,5-triClPh 2-187 3,4-diCH ₃ OPh Ph 2-FPh 2-188 3,4-diEtOPh Ph 3-FPh 2-189 3-CH ₃ OPh 4-ClPh 4-FPh 2 -190 3-EtOPh 4-BrPh 3,4,5-triFPh 2-191 4-CH ₃ OPh 4-FPh 2-BrPh 2-192 4-EtOPh 4-ClPh 3-BrPh 2-193 3,4-diCH ₃ OPh 4-FPh 4-BrPh 2-194 3,4-diEtOPh 4-BrPh 3,4,5-triBrPh 2-195 3-CH ₃ OPh 4- CH ₃ Ph 2-ClPh 2-196 3-EtOPh 4-CH ₃ Ph 3-ClPh 2-197 4-CH ₃ OPh 4-CH ₃ Ph 4-ClPh 2-198 4-EtOPh 4-CH ₃ Ph 3,4 , 5-triClPh 2-199 3,4-diCH ₃ OPh 4-CH ₃ Ph 2-FPh 2-200 3,4-diEtOPh 4-CH ₃ Ph 3-FPh 2-201 3-CH ₃ OPh 4-CF ₃ Ph 4-FPh 2-202 3-EtOPh 4-CF ₃ Ph 3,4,5-triFPh 2-203 4-CH ₃ OPh 4-CF ₃ Ph 2-BrPh 2-204 4-EtOPh 4-CF ₃ Ph 3 -BrPh 2-205 3,4-diCH ₃ OPh 4-CF ₃ Ph 4-BrPh 2 -206 3,4-diEtOPh 4-CF ₃ Ph 3,4,5-triBrPh 2-207 3-CH ₃ OPh 3, 4-diClPh 2-ClPh 2-208 3-EtOPh 3,4-diFPh 3-ClPh 2-209 4-CH ₃ OPh 3,4-diFPh 4-ClPh 2-210 4-EtOPh 3,4-diClPh 3,4 , 5-triClPh 2-211 3,4-diCH ₃ OPh 3,4-diClPh 2-FPh 2-212 3,4-diEtOPh 3,4-diFPh 3-FPh 2-213 4-CH ₃ OPh 3-ClPh 2 -Pyr 2-214 4-CH ₃ OPh 3-ClPh 3-Pyr 2-215 4-CH ₃ OPh 3-ClPh 4-Pyr 2-216 3-CH ₃ OPh 3-ClPh 3-Pyr 2-217 3,4 -diCH ₃ OPh 3-ClPh 3-Pyr 2-218 3-ClPh 3-ClPh 3-Pyr 2-219 4-EtOPh 3-ClPh 3-Pyr 2-220 4-PrOPh 3-ClPh 3-Pyr 2-221 3 -CH ₃ Ph 3-ClPh 3-Pyr 2-222 4-CH ₃ Ph 3-ClPh 3-Pyr 2-223 4-EtPh 3-ClPh 3-Pyr 2-224 3,4 -diCH ₃ Ph 3-ClPh 3-Pyr 2-225 3-CH ₃ OPh 3,5-diClPh 3-Pyr 2-226 4-CH ₃ OPh 3,5-diClPh 3-Pyr 2-227 3-EtOPh 3, 5-diClPh 3-Pyr 2-228 4-EtOPh 3,5-diClPh 3-Pyr 2-229 3-PrOPh 3,5-diClPh 3-Pyr 2-230 4-PrOPh 3,5-diClPh 3-Pyr 2- 231 3,4-diCH ₃ OPh 3,5-diClPh 3-Pyr 2-232 3-CH ₃ Ph 3,5-diClPh 3-Pyr 2-233 4-CH ₃ Ph 3,5-diClPh 3-Pyr 2-- 234 3-EtPh 3,5-diClPh 3-Pyr 2-235 4-EtPh 3,5-diClPh 3-Pyr 2-236 3-PrPh 3,5-diClPh 3-Pyr 2-237 4-PrPh 3,5- diClPh 3-Pyr 2-238 3,4-diCH ₃ Ph 3,5-diClPh 3-Pyr 2-239 4-CH ₃ OPh 3,5-diClPh 2-Pyr 2-240 4-CH ₃ OPh 3,5- diClPh 4-Pyr 2-241 4-CH ₃ OPh 2,3-diClPh 3-Pyr 2-242 4-CH ₃ OPh 2,5-diClPh 3-Pyr 2-243 4-CH ₃ OPh 2,6-diClPh 3 -Pyr 2-244 4-CH ₃ OPh 3,5-diCH ₃ Ph 3-Pyr 2-245 3-ClPh 3,5-diCH ₃ Ph 3-Pyr 2-246 4-ClPh 3,5-diCH ₃ Ph 3 -Pyr 2-247 3-FPh 3,5-diCH ₃ Ph 3-Pyr 2-248 4-FPh 3,5-diCH ₃ Ph 3-Pyr 2-249 4-EtPh 3,5-diCH ₃ Ph 3-Pyr 2-250 4-CH ₃ OPh 3,5-diCF ₃ Ph 3-Pyr 2-251 3-ClPh 3,5-diCF ₃ Ph 3-Pyr 2-252 4-ClPh 3,5-diCF ₃ Ph 3-Pyr 2-253 3-FPh 3,5-diCF ₃ Ph 3-Pyr 2-254 4-FPh 3,5-diCF ₃ Ph 3-Pyr 2-255 4-CH ₃ OPh 3-FPh 3-Pyr 2 -256 4-EtOPh 3-FPh 3-Pyr 2-257 4-EtPh 3-FPh 3-Pyr 2-258 4-PrPh 3-FPh 3-Pyr 2-259 4-CH ₃ OPh 3,5-diFPh 3- Pyr 2-260 4-EtOPh 3,5-diFPh 3-Pyr 2-261 4-CH ₃ OPh 3-CN-Ph 3-Pyr 2-262 4-EtOPh 3-CN-Ph 3-Pyr 2-263 4- EtPh 3-CN-Ph 3-Pyr 2-264 4-PrPh 3-CN-Ph 3-Pyr 2-265 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 2-266 4-EtOPh 3 -Cl-5-CH ₃ Ph 3-Pyr 2-277 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ Pyr) 2-278 4-EtOPh 3-ClPh 3- (2-CH ₃ Pyr) 2 -279 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ Pyr) 2-280 4-EtOPh 3-FPh 3- (2-CH ₃ Pyr) 2-281 4-CH ₃ OPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2-282 4-EtOPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2-283 4-EtPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2 -284 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ Pyr) 2-285 4-EtOPh 3,5-diFPh 3- (2-CH ₃ Pyr) 2-286 4-CH ₃ OPh 3 , 5-diClPh 3- (6-CH ₃ Pyr) 2-287 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 2-288 4-CH ₃ OPh 3,5-diClPh 3- (2 -ClPyr) 2-288 4-CH ₃ OPh 3,5-diClPh 3- (6-ClPyr) 2-289 4-CH ₃ OPh 3,5-diClPh 3- (2-FPyr) 2-290 4-CH ₃ OPh 3,5-diClPh 3- (2,4-diCH ₃ Pyr) 2-291 4-CH ₃ OPh 3 , 5-diClPh 3- (2-CH ₃ SPyr) 2-292 4-CH ₃ OPh 3,5-diClPh 3- (2-EtSPyr) 2-293 4-EtOPh 3,5-diClPh 3- (6-CH ₃ Pyr) 2-294 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 2-295 4-EtOPh 3,5-diClPh 3- (2-ClPyr) 2-296 4-EtOPh 3,5-diClPh 3- (6-ClPyr) 2-297 4-EtOPh 3,5-diClPh 3- (2-FPyr) 2-298 4-EtOPh 3,5-diClPh 3- (2,4-diCH ₃ Pyr) 2-299 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 2-300 4-EtOPh 3,5-diClPh 3- (2-EtSPyr) 2-301 4-CH ₃ OPh 3-ClPh 3- (6 -CH ₃ Pyr) 2-302 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 2-303 4-CH ₃ OPh 3-ClPh 3- (2-ClPyr) 2-304 4-CH ₃ OPh 3 -ClPh 3- (6-ClPyr) 2-305 4-CH ₃ OPh 3-ClPh 3- (2-FPyr) 2-306 4-CH ₃ OPh 3-ClPh 3- (2,4-diCH ₃ Pyr) 2 -307 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 2-308 4-CH ₃ OPh 3-ClPh 3- (2-EtSPyr) 2-309 4-EtOPh 3-ClPh 3- (6 -CH ₃ Pyr) 2-310 4-EtOPh 3-ClPh 3- (5-BrPyr) 2-311 4-EtOPh 3-ClPh 3- (2-ClPyr) 2-312 4-EtOPh 3-ClPh 3- (6 -ClPyr) 2-313 4-EtOPh 3-ClPh 3- (2-FPyr) 2-314 4-EtOPh 3-ClPh 3- (2,4-diCH ₃ Pyr) 2-315 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 2-316 4-EtOPh 3-ClPh 3- (2-EtSPyr ) 2-317 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 2-318 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 2-319 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 2-320 4-CH ₃ OPh 3,5-diFPh 3- (6-ClPyr) 2-321 4-CH ₃ OPh 3,5-diFPh 3- (2 -FPyr) 2-322 4-CH ₃ OPh 3,5-diFPh 3- (2,4-diCH ₃ Pyr) 2-323 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 2 -324 4-CH ₃ OPh 3,5-diFPh 3- (2-EtSPyr) 2-325 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 2-326 4-EtOPh 3-FPh 3- (5 -BrPyr) 2-327 4-EtOPh 3-FPh 3- (2-ClPyr) 2-328 4-EtOPh 3-FPh 3- (6-ClPyr) 2-329 4-EtOPh 3-FPh 3- (2-FPyr ) 2-330 4-EtOPh 3-FPh 3- (2,4-diCH ₃ Pyr) 2-331 4-EtOPh 3-FPh 3- (2-CH ₃ SPyr) 2-332 4-EtOPh 3-FPh 3- (2-EtSPyr) 2-333 4-CH ₃ OPh 3-CN-Ph 3- (6-CH ₃ Pyr) 2-334 4-CH ₃ OPh 3-CN-Ph 3- (5-BrPyr) 2-335 4-CH ₃ OPh 3-CN-Ph 3- (2-ClPyr) 2-336 4-CH ₃ OPh 3-CN-Ph 3- (6-ClPyr) 2-337 4-CH ₃ OPh 3-CN-Ph 3- (2-FPyr) 2-338 4-CH ₃ OPh 3-CN-Ph 3- (2,4-diCH ₃ Pyr) 2-339 4-CH ₃ OPh 3 -CN-Ph 3- (2-CH ₃ SPyr) 2-340 4-CH ₃ OPh 3-CN-Ph 3- (2-EtSPyr) 2-341 4-EtOPh 3-CN-Ph 3- (6-CH ₃ Pyr) 2-342 4-EtOPh 3-CN-Ph 3- (5-BrPyr) 2-343 4-EtOPh 3-CN-Ph 3- (2-ClPyr) 2-344 4-EtOPh 3-CN-Ph 3- (6-ClPyr) 2-345 4-EtOPh 3-CN-Ph 3- (2-FPyr) 2-346 4-EtOPh 3-CN-Ph 3- (2,4-diCH ₃ Pyr) 2-347 4-EtOPh 3-CN-Ph 3- (2-CH ₃ SPyr) 2-348 4-EtOPh 3-CN-Ph 3- (2-EtSPyr) 2-349 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ Pyr) 2-350 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2-351 4-CH ₃ OPh 3-Cl-5 -CH ₃ Ph 3- (5-BrPyr) 2-352 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 2-353 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-ClPyr) 2-354 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-FPyr) 2-355 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2,4-diCH ₃ Pyr) 2-356 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 2-357 4-CH ₃ OPh 3-Cl-5 -CH ₃ Ph 3- (2-EtSPyr) 2-358 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ Pyr) 2-359 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2-360 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 2-361 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2 -ClPyr) 2-362 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-ClPyr) 2-363 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-FPyr) 2-364 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2 , 4-diCH ₃ Pyr) 2-365 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 2-366 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2 -EtSPyr) 2-367 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 2-368 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2-369 4- CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 2-370 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr) 2-371 4-CH ₃ OPh 3-CN-Ph 3- (5-CH ₃ OPyr) 2-372 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 2-373 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 2-374 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2-375 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 2-376 4-EtOPh 3,5 -diFPh 3- (5-CH ₃ OPyr) 2-377 4-EtOPh 3-CN-Ph 3- (5-CH ₃ OPyr) 2-378 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) ──────────────────────────────────── Table 3

[0035]

[Chemical 7]

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound number R¹ R² R^Four ──────────────────────────────────── 3 -1 Ph 3,4-diCH₃OPh 3,4,5-triCH₃OPh 3 -2 3-ClPh 3,4-diCH₃OPh 3,4,5-triCH₃OPh 3 -3 3-CF₃Ph 3,4-diCH₃OPh 3,4,5-triCH₃OPh 3 -4 3-CH₃Ph 3,4-diCH₃OPh 3,4,5-triCH₃OPh 3 -5 4-CH₃OPh 3,4-diClPh 3,4,5-triCH₃OPh 3 -6 4-CH₃OPh 3,4-diCH₃Ph 3,4,5-triCH₃OPh 3 -7 3-ClPh 3-ClPh 3,4,5-triCH₃OPh 3 -8 3-CH₃Ph 3-CH₃Ph 3,4,5-triCH₃OPh 3 -9 3-ClPh 4-PrOPh 3,4,5-triCH₃OPh 3-10 3-ClPh 4-i-BuOPh 3,4,5-triCH₃OPh 3-11 3-CH₃Ph 4-PrOPh 3,4,5-triCH₃OPh 3-12 3-CH₃Ph 4-i-BuOPh 3,4,5-triCH₃OPh 3-13 3,4-diClPh 4-PrOPh 3,4,5-triCH₃OPh 3-14 3,4-diClPh 4-i-BuOPh 3,4,5-triCH₃OPh 3-15 3,4-diClPh 4-CH₃Ph 3,4,5-triCH₃OPh 3-16 3,4-diClPh 4-i-BuPh 3,4,5-triCH₃OPh 3-17 Ph 3,4-diCH₃OPh 3,4-diCH₃OPh 3-18 3-ClPh 3,4-diCH₃OPh 3,4-diCH₃OPh 3-19 3-CF₃Ph 3,4-diCH₃OPh 3,4-diCH₃OPh 3-20 3-CH₃Ph 3,4-diCH₃OPh 3,4-diCH₃OPh 3-21 4-CH₃OPh 3,4-diClPh 3,4-diCH₃OPh 3-22 4-CH₃OPh 3,4-diCH₃Ph 3,4-diCH₃OPh 3-23 3-ClPh 3-ClPh 3,4-diCH₃OPh 3-24 3-CH₃Ph 3-CH₃Ph 3,4-diCH₃OPh 3-25 3-ClPh 4-PrOPh 3,4-diCH₃OPh 3-26 3-ClPh 4-i-BuOPh 3,4-diCH₃OPh 3-27 3-CH₃Ph 4-PrOPh 3,4-diCH₃OPh 3-28 3-CH₃Ph 4-i-BuOPh 3,4-diCH₃OPh 3-29 3,4-diClPh 4-PrOPh 3,4-diCH₃OPh 3-30 3,4-diClPh 4-i-BuOPh 3,4-diCH₃OPh 3-31 3,4-diClPh 4-CH₃Ph 3,4-diCH₃OPh 3-32 3,4-diClPh 4-i-BuPh 3,4-diCH₃OPh 3-33 Ph 3,4-diCH₃OPh 4-CH₃OPh 3-34 3-ClPh 3,4-diCH₃OPh 4-CH₃OPh 3-35 3-CF₃Ph 3,4-diCH₃OPh 4-CH₃OPh 3-36 3-CH₃Ph 3,4-diCH₃OPh 4-CH₃OPh 3-37 4-CH₃OPh 3,4-diClPh 4-CH₃OPh 3-38 4-CH₃OPh 3,4-diCH₃Ph 4-CH₃OPh 3-39 3-ClPh 3-ClPh 4-CH₃OPh 3-40 3-CH₃Ph 3-CH₃Ph 4-CH₃OPh 3-41 3-ClPh 4-PrOPh 4-CH₃OPh 3-42 3-ClPh 4-i-BuOPh 4-CH₃OPh 3-43 3-CH₃Ph 4-PrOPh 4-CH₃OPh 3-44 3-CH₃Ph 4-i-BuOPh 4-CH₃OPh 3-45 3,4-diClPh 4-PrOPh 4-CH₃OPh 3-46 3,4-diClPh 4-i-BuOPh 4-CH₃OPh 3-47 3,4-diClPh 4-CH₃Ph 4-CH₃OPh 3-48 3,4-diClPh 4-i-BuPh 4-CH₃OPh 3-49 Ph 3-CH₃O-4-PrOPh 3,4,5-triCH₃OPh 3-50 Ph 3,4-diPrOPh 3,4,5-triCH₃OPh 3-51 Ph 3-PrO-4-CH₃OPh 3,4,5-triCH₃OPh 3-52 3-ClPh 3-CH₃O-4-PrOPh 3,4,5-triCH₃OPh 3-53 3-ClPh 3-PrO-4-CH₃OPh 3,4,5-triCH₃OPh 3-54 3-ClPh 3,4-diPrOPh 3,4,5-triCH₃OPh 3-55 3-ClPh 3-CH₃OPh 3,4,5-triCH₃OPh 3-56 3-CH₃Ph 3-CH₃O-4-PrOPh 3,4,5-triCH₃OPh 3-57 3-CH₃Ph 3-PrO-4-CH₃OPh 3,4,5-triCH₃OPh 3-58 3-CH₃Ph 3,4-diPrOPh 3,4,5-triCH₃OPh 3-59 3-CF₃Ph 3-CH₃O-4-PrOPh 3,4,5-triCH₃OPh 3-60 3-CF₃Ph 3-PrO-4-CH₃OPh 3,4,5-triCH₃OPh 3-61 3-CF₃Ph 3,4-diPrOPh 3,4,5-triCH₃OPh 3-62 3-BrPh 3-CH₃O-4-PrOPh 3,4,5-triCH₃OPh 3-63 3-BrPh 3-PrO-4-CH₃OPh 3,4,5-triCH₃OPh 3-64 3-BrPh 3,4-diPrOPh 3,4,5-triCH₃OPh 3-65 3-BrPh 3-CH₃OPh 3,4,5-triCH₃OPh 3-66 3-BrPh 3-PrOPh 3,4,5-triCH₃OPh 3-67 3-BrPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-68 3-BrPh 4-EtOPh 3,4,5-triCH₃OPh 3-69 3-BrPh 4-PrOPh 3,4,5-triCH₃OPh 3-70 3-BrPh 4-BuOPh 3,4,5-triCH₃OPh 3-71 3-CF₃Ph 3-CH₃OPh 3,4,5-triCH₃OPh 3-72 3-CF₃Ph 4-CH₃OPh 3,4,5-triCH₃OPh 3-73 3-CF₃Ph 3-PrOPh 3,4,5-triCH₃OPh 3-74 3-CF₃Ph 4-PrOPh 3,4,5-triCH₃OPh 3-75 3-F-Ph 3-CH₃OPh 3,4,5-triCH₃OPh 3-76 3-F-Ph 4-CH₃OPh 3,4,5-triCH₃OPh 3-77 3-F-Ph 3-PrOPh 3,4,5-triCH₃OPh 3-78 3-F-Ph 4-PrOPh 3,4,5-triCH₃OPh 3-79 3,5-diClPh 3-CH₃OPh 3,4,5-triCH₃OPh 3-80 3,5-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-81 3,5-diClPh 3-PrOPh 3,4,5-triCH₃OPh 3-82 3,5-diClPh 4-PrOPh 3,4,5-triCH₃OPh 3-83 3-ClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-84 2,3-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-85 2,4-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-86 2,5-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-87 2,6-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh 3-88 3,6-diClPh 4-CH₃OPh 3,4,5-triCH₃OPh ──────────────────────────────────── Table 4

[0037]

[Chemical 8]

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound number R ¹ R ² R ⁴ p ── ────────────────────────────────── 4-1 4-ClPh 4-ClPh 3,4,5-triCH ₃ OPh 1 4-2 4-ClPh 4-ClPh 3,4,5-triCH ₃ OPh 2 4-3 4-ClPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-4 4-CH ₃ OPh 4 -CH ₃ OPh 3,4,5-triCH ₃ OPh 1 4-5 4-CH ₃ OPh 4-CH ₃ OPh 3,4,5-triCH ₃ OPh 2 4-6 4-CH ₃ OPh 3-ClPh 3, 4,5-triCH ₃ OPh 1 4-7 4-CH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-8 4-CH ₃ OPh 2,3-diClPh 3,4,5-triCH ₃ OPh 1 4-9 4-CH ₃ OPh 2,3-diClPh 3,4,5-triCH ₃ OPh 2 4-10 4-CH ₃ OPh 2,4-diClPh 3,4,5-triCH ₃ OPh 1 4- 11 4-CH ₃ OPh 2,4-diClPh 3,4,5-triCH ₃ OPh 2 4-12 4-CH ₃ OPh 2,5-diClPh 3,4,5-triCH ₃ OPh 1 4-13 4-CH ₃ OPh 2,5-diClPh 3,4,5-triCH ₃ OPh 2 4-14 4-CH ₃ OPh 2,6-diClPh 3,4,5-triCH ₃ OPh 1 4-15 4-CH ₃ OPh 2, _{6-diClPh 3,4,5-triCH 3 OPh} 2 _{-16 4-CH 3 OPh 3,4-} diClPh 3,4,5-triCH 3 OPh 1 4-17 4-CH 3 OPh 3,4-diClPh 3,4,5-triCH 3 OPh 2 4-18 4- CH ₃ OPh 3,5-diClPh 3,4,5-triCH ₃ OPh 1 4-19 4-CH ₃ OPh 3,5-diClPh 3,4,5-triCH ₃ OPh 2 4-20 4-CH ₃ OPh 3 -FPh 3,4,5-triCH ₃ OPh 1 4-21 4-CH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-22 4-CH ₃ OPh 3,5-diFPh 3,4, 5-triCH ₃ OPh 1 4-23 4-CH ₃ OPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-24 4-CH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 1 4-25 4-CH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-26 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 4- 27 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-28 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 1 4- 29 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-30 4-EtOPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-31 4-EtOPh 3-ClPh 3 , 4,5-triCH ₃ OPh 2 4-32 4-EtOPh 2,3-diClPh 3,4,5-triCH ₃ OPh 1 4-33 4-EtOPh 2,3-diClPh 3,4,5-triCH ₃ OPh 2 4-34 4-EtOPh 2,4-diClPh 3,4,5-triCH ₃ OPh 1 4-35 4-EtOPh 2,4-diClPh 3,4,5-triCH ₃ OPh 2 4-36 4-EtOPh 2 , 5-di ClPh 3,4,5-triCH ₃ OPh 1 4-37 4-EtOPh 2,5-diClPh 3,4,5-triCH ₃ OPh 2 4-38 4-EtOPh 2,6-diClPh 3,4,5-triCH ₃ OPh 1 4-39 4-EtOPh 2,6-diClPh 3,4,5-triCH ₃ OPh 2 4-40 4-EtOPh 3,4-diClPh 3,4,5-triCH ₃ OPh 1 4-41 4- EtOPh 3,4-diClPh 3,4,5-triCH ₃ OPh 2 4-42 4-EtOPh 3,5-diClPh 3,4,5-triCH ₃ OPh 1 4-43 4-EtOPh 3,5-diClPh 3, 4,5-triCH ₃ OPh 2 4-44 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 1 4-45 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-46 4 -EtOPh 3,5-diFPh 3,4,5-triCH ₃ OPh 1 4-47 4-EtOPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-48 4-EtOPh 3-CNPh 3,4 , 5-triCH ₃ OPh 1 4-49 4-EtOPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-50 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 4-51 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-52 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 1 4-53 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-54 4-CH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-55 4-CH ₃ OPh 3,5 -diClPh 3,4,5-triCH ₃ OPh 3 4-56 4-CH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 3 4-57 4-CH ₃ OPh 3,5-diFPh 3,4,5-triCH ₃ OPh 3 4-58 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-59 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 3 4-60 4-EtOPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-61 4-EtOPh 3,5-diClPh 3,4,5-triCH ₃ OPh 3 4-62 4-EtOPh 2,5-diClPh 3,4,5-triCH ₃ OPh 3 4-63 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 3 4-64 4-EtOPh 3,5- diFPh 3,4,5-triCH ₃ OPh ₃ 4-65 4-EtOPh 3-CNPh 3,4,5-triCH ₃ OPh 3 4-66 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5 -triCH ₃ OPh 3 4-67 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 3 4-68 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 14 -69 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-70 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-71 4- CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 1 4-72 4-CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-73 4- CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-74 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 4-75 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-76 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-77 4-EtOPh 3,5-diCH ₃ Ph 3,4, 5-triCH ₃ OPh 1 4-78 4-EtOPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-79 4-EtOPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-80 3,4-diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-81 3,4-diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-82 3,4- diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-83 3,4-diCH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 1 4-84 3,4-diCH ₃ OPh 3 -FPh 3,4,5-triCH ₃ OPh 2 4-85 3,4-diCH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 3 4-86 3,4-diCH ₃ OPh 3-CNPh 3, 4,5-triCH ₃ OPh 1 4-87 3,4-diCH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-88 3,4-diCH ₃ OPh 3-CNPh 3,4,5- triCH ₃ OPh 3 4-89 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 1 4-90 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 2 4-91 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 3 4-92 4-EtPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-93 4- EtPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-94 4-EtPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-95 4-EtPh 3,5-diClPh 3,4,5- triCH ₃ OPh 1 4-96 4-EtPh 3,5-diClPh 3,4,5-triCH ₃ OPh 2 4-97 4-EtPh 3,5-diClPh 3,4,5-triCH ₃ OPh 3 4-98 4 -EtPh 2,5-diClPh 3,4,5-triCH ₃ OPh 1 4-99 4-EtPh 2,5-diClPh 3,4,5-triCH ₃ OPh 2 4-100 4-EtPh 2,5-diClPh 3,4 , 5-triCH ₃ OPh 3 4-101 4-EtPh 3-FPh 3,4,5-triCH ₃ OPh 1 4-102 4-EtPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-103 4- EtPh 3-FPh 3,4,5-triCH ₃ OPh 3 4-104 4-EtPh 3,5-diFPh 3,4,5-triCH ₃ OPh 1 4-105 4-EtPh 3,5-diFPh 3,4, 5-triCH ₃ OPh 2 4-106 4-EtPh 3,5-diFPh 3,4,5-triCH ₃ OPh 3 4-107 4-EtPh 3-CNPh 3,4,5-triCH ₃ OPh 1 4-108 4 -EtPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-109 4-EtPh 3-CNPh 3,4,5-triCH ₃ OPh 3 4-110 4-EtPh 3-CF ₃ Ph 3,4,5 -triCH ₃ OPh 1 4-111 4-EtPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-112 4-EtPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 3 4-113 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 4-114 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-115 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 3 4-116 4-PrPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-117 4-PrPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-118 4-PrPh 3,5-diClPh 3,4,5-triCH ₃ OPh 1 4-119 4-PrPh 3,5-diClPh 3,4,5-triCH ₃ OPh 2 4-120 4-PrPh 3-FPh 3,4,5-triCH ₃ OPh 1 4-121 4-PrPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-122 4-PrPh 3,5 -diFPh 3,4,5-triCH ₃ OPh 1 4-123 4-PrPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-124 4-PrPh 3-CNPh 3,4,5-triCH ₃ OPh 1 4-125 4-PrPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-126 4-PrPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 1 4-127 4-PrPh 3- CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-128 4-PrPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 1 4-129 4-PrPh 3-Cl-5- CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-130 4-CH ₃ OPh 3-ClPh 3-Pyr 1 4-131 4-CH ₃ OPh 3-ClPh 3-Pyr 2 4-132 4-CH ₃ OPh 3-ClPh 3-Pyr 3 4-133 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 1 4-134 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 2 4-135 4 -CH ₃ OPh 3-ClPh 3- (5-BrPyr) 3 4-136 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 1 4-137 4-CH ₃ OPh 3-ClPh 3- ( 5-CH ₃ OPyr) 2 4-138 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 3 4-139 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 1 4 -140 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 2 4-141 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 3 4-142 4-CH ₃ OPh 3-ClPh 3- (6-CH ₃ Pyr) 1 4-143 4-CH ₃ OPh 3-ClPh 3- (6-CH ₃ Pyr) 2 4-144 4-CH ₃ OPh 3-ClPh 3- ( 6-CH ₃ Pyr) 3 4-145 4-CH ₃ OPh 3,5-diClPh 3-Pyr 1 4-146 4-CH ₃ OPh 3,5-diClPh 3-Pyr 2 4-147 4-CH ₃ OPh 3 , 5-diClPh 3-Pyr 3 4-148 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 1 4-149 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 2 4-150 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 3 4-151 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 1 4-152 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2 4-153 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 3 4-154 4-CH ₃ OPh 3, 5-diClPh 3- (2-CH ₃ SPyr) 1 4-155 4-CH ₃ OPh 3,5-diClPh 3- (2-CH ₃ SPyr) 2 4-156 4-CH ₃ OPh 3,5-diClPh 3 -(2-CH ₃ SPyr) ₃ 4-157 4-CH ₃ OPh 3,5-diClPh 3- (6-CH ₃ Pyr) 1 4-158 4-CH ₃ OPh 3,5-diClPh 3- (6- CH ₃ Pyr) 2 4-159 4-CH ₃ OPh 3,5-diClPh 3- (6-CH ₃ Pyr) 3 4-160 4-CH ₃ OPh 3-FPh 3-Pyr 1 4-161 4-CH ₃ OPh 3-FPh 3-Pyr 2 4-162 4-CH ₃ OPh 3-FPh 3-Pyr ₃ 4-163 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 1 4-164 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 2 4-165 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 3 4-166 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 1 4-167 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 2 4-168 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 3 4-169 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 1 4-170 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 2 4-171 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 3 4-172 4- CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 1 4-173 4-CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 2 4-174 4-CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 3 4-175 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 1 4-176 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 2 4-177 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 3 4-178 4-CH ₃ OPh 3,5-diFPh 3-Pyr 1 4-179 4-CH ₃ OPh 3,5- diFPh 3-Pyr 2 4-180 4-CH ₃ OPh 3,5-diFPh 3-Pyr 3 4-181 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 1 4-182 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 2 4-183 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 3 4-184 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 1 4-185 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 2 4-186 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 3 4- 187 4-CH ₃ OPh 3,5-diFPh 3- (5 -CH ₃ OPyr) 1 4-188 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr) 2 4-189 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr ) 3 4-190 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 1 4-191 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 2 4- 192 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 3 4-193 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 1 4-194 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 2 4-195 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 3 4-196 4-CH ₃ OPh 3- CNPh 3-Pyr 1 4-197 4-CH ₃ OPh 3-CNPh 3-Pyr 2 4-198 4-CH ₃ OPh 3-CNPh 3-Pyr 3 4-199 4-CH ₃ OPh 3-CNPh 3- (2 -ClPyr) 1 4-200 4-CH ₃ OPh 3-CNPh 3- (2-ClPyr) 2 4-201 4-CH ₃ OPh 3-CNPh 3- (2-ClPyr) 3 4-202 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 1 4-203 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 2 4-204 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 3 4 -205 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 1 4-206 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 2 4-207 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 3 4-208 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 1 4-209 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 2 4- 210 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 3 4-211 4-CH ₃ OPh 3-CNPh 3- (6-CH ₃ Pyr) 1 4-212 4-CH ₃ OPh 3-CNPh 3- (6 -CH ₃ Pyr) 2 4-213 4-CH ₃ OPh 3-CNPh 3- (6-CH ₃ Pyr) 3 4-214 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 1 4- 215 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 2 4-216 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 3 4-217 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (2-ClPyr) 1 4-218 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 2 4-219 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (2-ClPyr) 3 4-220 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 1 4-221 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (5-BrPyr) 2 4-222 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 3 4-223 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 1 4-224 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 2 4-225 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 3 4-226 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 1 4- 227 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 2 4-228 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr ) 3 4-229 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 1 4-230 4-CH ₃ OPh 3-Cl- 5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2 4-231 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 3 4-232 4-EtOPh 3- ClPh 3-Pyr 1 4-233 4-EtOPh 3-ClPh 3-Pyr 2 4-234 4-EtOPh 3-ClPh 3-Pyr 3 4-235 4-EtOPh 3-ClPh 3- (2-ClPyr) 1 4- 236 4-EtOPh 3-ClPh 3- (2-ClPyr) 2 4-237 4-EtOPh 3-ClPh 3- (2-ClPyr) 3 4-238 4-EtOPh 3-ClPh 3- (5-BrPyr) 14 -239 4-EtOPh 3-ClPh 3- (5-BrPyr) 2 4-240 4-EtOPh 3-ClPh 3- (5-BrPyr) 3 4-241 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr ) 1 4-242 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 2 4-243 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 3 4-244 4-EtOPh 3-ClPh 3 -(2-CH ₃ SPyr) 1 4-245 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 2 4-246 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 3 4-247 4-EtOPh 3-ClPh 3- (6-CH ₃ Pyr) 1 4-248 4-EtOPh 3-ClPh 3- (6-CH ₃ Pyr) 2 4-249 4-EtOPh 3-ClPh 3- (6-CH ₃ Pyr) 3 4-250 4-EtOPh 3,5-diClPh 3-Pyr 1 4-251 4-EtOPh 3,5-diClPh 3-Pyr 2 4-252 4-EtOPh 3,5-diClPh 3-Pyr 3 4 -253 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 1 4-254 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 2 4- 255 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 3 4-256 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 1 4-257 4-EtOPh 3,5-diClPh 3 -(5-CH ₃ OPyr) 2 4-258 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 3 4-259 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 1 4-260 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 2 4-261 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 3 4-262 4-EtOPh 3 , 5-diClPh 3- (6-CH ₃ Pyr) 1 4-263 4-EtOPh 3,5-diClPh 3- (6-CH ₃ Pyr) 2 4-264 4-EtOPh 3,5-diClPh 3- (6 -CH ₃ Pyr) 3 4-265 4-EtOPh 3-FPh 3-Pyr 1 4-266 4-EtOPh 3-FPh 3-Pyr 2 4-267 4-EtOPh 3-FPh 3-Pyr 3 4-268 4- EtOPh 3-FPh 3- (2-ClPyr) 1 4-269 4-EtOPh 3-FPh 3- (2-ClPyr) 2 4-270 4-EtOPh 3-FPh 3- (2-ClPyr) 3 4-2714 -EtOPh 3-FPh 3- (5-BrPyr) 1 4-272 4-EtOPh 3-FPh 3- (5-BrPyr) 2 4-273 4-EtOPh 3-FPh 3- (5-BrPyr) 3 4-274 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 1 4-275 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 2 4-276 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 3 4-277 4-EtOPh 3-FPh 3- (2-CH ₃ SPh) 1 4-278 4-EtOPh 3-FPh 3- (2-CH ₃ SPh) 2 4-279 4 -EtOPh 3-FPh 3- (2-CH ₃ SPh) 3 4-280 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 1 4-281 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 2 4-282 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 3 4-283 4-EtOPh 3-CNPh 3-Pyr 1 4-284 4-EtOPh 3-CNPh 3-Pyr 2 4- 285 4-EtOPh 3-CNPh 3-Pyr 3 4-286 4-EtOPh 3-CNPh 3- (5-BrPyr) 1 4-287 4-EtOPh 3-CNPh 3- (5-BrPyr) 2 4-288 4- EtOPh 3-CNPh 3- (5-BrPyr) 3 4-289 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 1 4-290 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 2 4-291 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 3 4-292 4-EtOPh 3-CNPh 3- (2-CH ₃ SPyr) 1 4-293 4-EtOPh 3-CNPh 3- ( 2-CH ₃ SPyr) 24 4-294 4-EtOPh 3-CNPh 3- (2-CH ₃ SPyr) 3 4-295 4-EtOPh 3-CNPh 3- (6-CH ₃ SPyr) 1 4-296 4- EtOPh 3-CNPh 3- (6-CH ₃ SPyr) 2 4-297 4-EtOPh 3- (6-CH ₃ SPyr) 3 4-298 4-EtOPh 3-Cl-5-CH ₃ Ph 3- Pyr 1 4-299 4-EtOPh 3-Cl-5-CH ₃ Ph 3-Pyr 2 4-300 4-EtOPh 3-Cl-5-CH ₃ Ph 3-Pyr 3 4-301 4-EtOPh 3-Cl- 5-CH ₃ Ph 3- (2-ClPyr) 1 4-302 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 2 4-303 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 3 4-304 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 1 4-305 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 2 4-306 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 3 4-306 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr ) 3 4-307 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPh) 1 4-308 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPh ) 2 4-309 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPh) 3 4-310 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh ) 1 4-311 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh) 2 4-312 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh ) 3 4-313 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 1 4-314 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr ) 2 4-315 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 3 4-316 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 1 4-317 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 2 4-318 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 3 4-319 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 14 -320 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 2 4-321 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 3 ────────── ────────────────── ──────── Among the exemplified compounds described in Table 1, suitable compounds, 1,2,3,4,6,14,16,17,1
8, 19, 20, 25, 26, 28, 29, 30, 4
1,45,46,53,76,83,91,116,1
17,118,120,129,130,133,13
4,141,154,155,207,220,29
8,300,313,325,327,342,34
3,388,411,412,419,420,42
4,425,426,431,433,441,44
5,452,453,454,455,456,45
7,458,459,460,461,462,46
3,466,467,468,469,470,47
1,472,473,474,475,476,47
7,478,479,480,481,482,48
3,484,485,486,487,488,48
9,490,491,492,496,498,50
1,505,507,510,511,512,51
3,514, 515, 516, 517, 518, 51
9,520,521,522,523,524,52
5,528,529,530,531,536,53
7,539,541,546,551,552,55
3,556,557,558,559,560,56
1,562,563,564,565,566,56
7,568,569,570,571,572,57
3,574,580,581,582,583,58
4,585,586,587,588,589,59
0,591,592,593,594,595,59
6,598,601,602,603,604,60
5,606,607,608,609,610,61
1,612,616,621,622,623,62
4,625,626,627,628,629,63
0,631,632,633,634,635,63
6,637,638,639,640,641,64
2,643,644,645,646,647,64
9,650,651,652,655,659,66
0,661,662,663,664,665,66
6,667,668,669,670,671,67
2,673,674,675,676,677,67
8,679,680,681,682,683,68
4,685,686,687,688,689,69
0,691,692,693,694,695,69
6,697,699,700,701,702,70
3,704,705,706,707,708,70
9,710,711,712,713,714,71
5,716,717,718,719,720,72
1,722,723,724,725,726,72
7,728,729,730,731,732,73
3,734,735,736,737,738,73
9,740,741,742,743,744,74
5,746,747,748,749,750,75
1,752,753,754,755,756,75
7,758,759,760,761,762,76
3,764,766,771,772,773,77
4,777,778,779,780,781,78
2,783,784,785,787,788,78
9,790,793,795,796,798,79
9,801,803,805,807,809,81
0,813,815,817,820,821,82
3,825,832,833,845,846,85
0,851,858,859,860,862,86
3,866,867,871,872,873,87
The compounds of 4,875, 876, 877, 879 and 880 may be mentioned.

Among the exemplified compounds listed in Table 2 above,
Suitable compounds include 1,7,8,9,15,16,
19,21,23,24,25,29,30,31,3
2,35,37,41,44,45,46,47,5
1,53,57,59,62,65,66,67,6
8, 70, 72, 74, 75, 77, 78, 80, 8
3,84,85,86,87,88,89,90,9
1, 92, 93, 94, 101, 102, 103, 10
4,107,108,109,110,112,16
3,255,256,257,258,259,26
0,261,265,266,278,280,28
2,285,291,292,294,299,30
0,302,310,318,323,324,32
5,326,331,332,334,340,34
6,351,355,360,364,365,36
8,369,371,372,374,375,377
And 378 compounds can be mentioned.

Among the exemplified compounds listed in Table 3 above,
Suitable compounds include 1,2,3,4,5,6,7,
8, 9, 11, 13, 18, 19, 23, 25, 29,
34, 35, 37, 49, 50, 51, 52, 54, 5
The compounds of 6,58,59,61,62,64,67 and 68 may be mentioned.

Among the exemplified compounds listed in Table 4 above,
Suitable compounds include 1,2,4,5,7,8,1
0, 12, 13, 14, 16, 18, 19, 20, 2
1, 22, 24, 25, 26, 27, 28, 30, 3
2,36,37,38,42,43,44,45,4
6,48,49,50,51,63,65,83,8
6, 101, 102, 107, 118, 121, 12
4,130,131,134,145,148,16
0,166,167,169,178,184,19
4,202,205,214,220,223,23
2,238,241,250,253,265,26
6,271,274,283,286,289,29
The compounds of 8,304 and 308 may be mentioned.

Of the exemplified compounds listed in Table 1 above,
More preferable compounds include 28,53,419,42
4,426,431,441,445,453,45
4,455,456,461,462,463,46
4,467,468,469,470,472,47
5,476,478,480,482,483,48
4,486,510,512,513,514,51
5,517,519,521,524,529,53
1,541,546,558,560,568,57
0,574,581,582,585,587,59
0,592,594,598,603,606,60
9,622,627,628,631,632,63
7,660,668,670,671,675,67
9,680,681,684,685,693,69
4,702,703,707,710,713,71
4,717,718,719,727,728,73
0,731,733,737,740,743,74
6,752,758,759,772,773,77
7,778,784,793,795,799,80
3,805,813,815,845,858,85
9,866,867,872,873,874,877
And 878 compounds.

Among the exemplified compounds listed in Table 2 above,
More preferable compounds include 255, 256, 260,
261, 262, 266, 294, 318, 326, 3
The compounds of 34, 351 and 360 may be mentioned.

Among the exemplified compounds listed in Table 3 above,
More preferable compounds include 2,3,5,49,50,
The compounds of 52, 54, 56 and 59 may be mentioned. Among the exemplified compounds listed in Table 4 above, more preferable compounds include 12,18,20,21,24,2.
5,26,27,36,42,44,45,48,13
The compounds of 0 and 286 can be mentioned.

Of the exemplified compounds shown in Tables 1 to 4, the most preferable compounds are 28,419,424,426,453,454,4 shown in Table 1.
55,467,468,469,470,482,48
3,484,513,515,529,557,55
9,574,590,594,603,606,62
2,627,685,710,740,743,79
3,803,805,858,859,872,87
The compounds of 3,874,877 and 878, the compounds of 256,262 and 326 listed in Table 2, and the compounds of 42,44 and 48 listed in Table 4 can be mentioned.

The N- (3,3-disubstituted acryloyl) piperazine derivative of the present invention can be produced by the method described below.

In the case of producing a compound having a thiocarbonyl group in the molecule, it is usually produced by the following reaction using a compound having a corresponding thiocarbonyl group as a starting material. It can also be produced by synthesizing a compound having a carbonyl group, and then reacting it according to a conventional method using a reagent such as Lawesson's reagent for converting a carbonyl group into a thiocarbonyl group. At this time, when the molecule has two carbonyl groups, two or one carbonyl group can be selectively converted to a thiocarbonyl group by selecting the conditions.

[Method A]

[0049]

[Chemical 9]

In the above formula, R ¹ , R ² , R ³ , R ⁴ , X and A have the same meanings as described above, and B is a general formula.

[0051]

[Chemical 10]

(Wherein R ⁵ , m and n have the same meanings as defined above), and Y represents a nucleophilic leaving group, such as chlorine, bromine or iodine. And a halogen atom; an azido group or a lower alkoxycarbonyloxy group such as methoxycarbonyloxy and ethoxycarbonyloxy.

[Method A] is a compound of the present invention in which R ³ and R ⁵ are not combined to form the general formula — (CH ₂ ) _p — (wherein p is 1 to 3). Is a manufacturing method.

In step A-1 , the carboxylic acid derivative (A
Is a step of converting I) into its activated derivative (AII). Activation is carried out according to a conventional method. When an acid halide compound is produced, it is carried out using a phosphorus chloride such as phosphorus pentachloride or phosphorus trichloride, or a sulfuric acid derivative such as thionyl chloride. Is carried out using an azidating agent such as diphenylphosphoryl azide (DPPA) and an organic base, and when a lower alkoxycarbonyloxy compound is prepared, a halogeno such as ethyl chlorocarbonate is prepared. It is carried out using a lower alkyl carbonate and an organic base. The organic base used above is not particularly limited as long as it is used as a base in a normal reaction, but preferably triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N -Dimethylamino) pyridine, N,
N-dimethylaniline, 1,5-diazabicyclo [4.3.0] nona
-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-
Mention may be made of organic bases such as diazabicyclo [5.4.0] undec-7-ene (DBU).

In the step A-2 , the activated carboxylic acid derivative (AII) and the compound (AIII) are dissolved in a solvent,
In this step, the compound (I) of the present invention is produced by reacting in the presence or absence of a base. When the activated carboxylic acid derivative (AII) is an acid halide compound, it is preferable to use a base, and the base used is
There is no particular limitation as long as it is used as a base in a usual reaction. For example, as a base, an alkali metal carbonate such as sodium carbonate or potassium carbonate; an alkali metal hydrogen carbonate such as sodium hydrogen carbonate or potassium hydrogen carbonate; an alkali metal carbonate such as lithium hydride, sodium hydride or potassium hydride Hydride; when using inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, barium hydroxide,
As solvents, ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide; sulfoxides such as dimethylsulfoxide; such as acetonitrile Nitriles; Water or a mixed solvent of water and the above organic solvent is preferably used, and as a base, triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N- Dimethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene,
When using organic bases such as 1,4-diazabicyclo [2.2.2] octane and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), it is recommended that benzene, toluene and xylene be used. It is preferable to use aromatic hydrocarbons; ethers such as ether, tetrahydrofuran, dioxane and dimethoxyethane, or halogenated hydrocarbons such as methylene chloride and chloroform.

Activated carboxylic acid derivative (AII)
When the is an acid azide compound or a lower alkoxycarbonyloxy compound, the reaction proceeds even in the absence of a base, and thus the above organic base is not always necessary. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the raw materials to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene and xylene;
Halogenated hydrocarbons such as methylene chloride and chloroform; ethers such as ether, tetrahydrofuran, dioxane and dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide; dimethyl sulfoxide Mention may be made of sulfoxides such as or nitriles such as acetonitrile. The reaction temperature is 0 ° C to 50 ° C, preferably room temperature, and the reaction time is usually 15 minutes to 1 day, varying mainly depending on the reaction temperature, the starting compound or the type of solvent used. Is.

The compound (AIII) used in the step A-2 is a known compound [for example, 1- (3,4,5
-Trimethoxybenzoyl) piperazine was prepared by Toldi et al. (Acta.Chim.Acad.Sci.Hung., 49 (3), 265-285 (19
66), 1- (3,4,5-trimethoxythiobenzoyl) piperazine was obtained by Farina et al. (Eur.Med.Chem.Chimica The
rapeutica, 14 (1), 27-31 (1979), manufactured. ] Or a compound (BI) and a compound (BI
It is produced by reacting II) according to the step B-2.

[Method B]

[0059]

[Chemical 11]

In the above formula, R ¹ , R ² , R ³ , R ⁴ , X,
Y, A and B have the same meaning as described above.

Also in the [Method B], the compound of the present invention in the case where R ³ and R ⁵ together do not represent the general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). Is a separate manufacturing method.

In the step B-1 , the activated carboxylic acid derivative (AII) and the compound (BI) are reacted according to the step A-2, and then the formyl group substituted on the nitrogen atom is removed. In this step, the compound (BII) is removed to produce compound (BII). The subsequent removal of the formyl group is achieved by treatment with a base in the presence of solvent. The base is not particularly limited as long as it does not affect other parts of the compound, but preferably metal alcohols such as sodium methoxide; alkali metal carbonates such as sodium carbonate and potassium carbonate. It is carried out using a salt; an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; aqueous ammonia or concentrated ammonia-methanol. The solvent used is not particularly limited as long as it can be used in a usual hydrolysis reaction, and water; methanol, ethanol,
Preference is given to alcohols such as n-propanol; organic solvents such as ethers such as tetrahydrofuran and dioxane, or mixed solvents of water and an organic solvent. The reaction temperature and reaction time vary depending on the starting material and the base used and are not particularly limited, but in order to suppress side reactions, it is generally carried out at 0 ° C to 150 ° C, preferably at room temperature, and the reaction time is preferably Is 1 to 24 hours.

The step B-2 is a step for producing the compound (I) of the present invention by reacting the compound (BII) with the compound (BIII) in a solvent in the presence of a base. When B represents a group other than a lower alkylene group, it is carried out according to the step A-2, and when B represents a lower alkylene group, preferably lithium hydride, sodium hydride, potassium hydride Alkali metal hydride such as is used, the solvent is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably ether, tetrahydrofuran, dioxane, dimethoxy Ethers such as ethane or amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide are used.

After completion of the reaction, the target compound for each reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding an organic solvent immiscible with water to the reaction mixture, washing with water and distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

[Method C]

[0066]

[Chemical formula 12]

In the above formula, R ¹ , R ² , R ⁴ , X, A,
Y, m, n and p have the same meanings as described above.

[Method C] is a compound of the present invention in which R ³ and R ⁵ are taken together to form the general formula — (CH ₂ ) _p — (wherein p is 1 to 3). It is a manufacturing method.

The step C-1 is carried out by using a bicyclic amine compound (C
The secondary amino group of I) is added to the compound (BIII) and a B-
It is a method of producing a compound (CII) in which a nitrogen atom is substituted by reacting according to two steps.

In the step C-2 , the compound (C
II) is treated with a base in the presence of a solvent to generate an anion in a methylene group adjacent to a carbonyl group, and then reacted with a compound (CIII) to carry out an aldol reaction to produce a compound (CIV). It is a process to do. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether; Aromatic hydrocarbons such as benzene, toluene, xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, dimethylformamide, dimethylacetamide, hexamethyl Examples thereof include amides such as phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane. The base used is not particularly limited as long as it is used as a base in a usual reaction, but preferably inorganic bases such as alkali metal hydrides such as sodium hydride and potassium hydride; Alkali metal alkoxides such as sodium methoxide and sodium ethoxide; 1,5-diazabicyclo [4.3.0] non-5-ene,
Organic bases such as 1,4-diazabicyclo [2.2.2] octane (DABCO) and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) or organics such as butyllithium and lithium diisopropylamide Mention may be made of metal bases. The reaction temperature is -78 ° C to 0 ° C, preferably -78 ° C to -50 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of solvent used, but it is usually 1 hour to 2 hours.

In the step C-3 , the compound (C
IV) is a step of producing the compound (CV) of the present invention by dehydrating IV) by treating with an acid or a dehydrating agent such as phosphorus oxychloride in the presence or absence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, aliphatic hydrocarbons such as hexane and heptane; benzene, toluene and xylene. Aromatic hydrocarbons such as; methylene chloride, halogenated hydrocarbons such as chloroform; esters such as ethyl acetate, propyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane; methanol; Alcohols such as alcohol and ethanol; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphorotriol Amides such as amides; dimethyl sulfoxide Can be exemplified de, sulfoxides such as sulfolane. When phosphorus oxychloride is used as the dehydrating agent, an aproton-donating solvent must be used among the above solvents, and preferably aliphatic hydrocarbons; aromatic hydrocarbons. Or halogenated hydrocarbons. The acid used is not particularly limited as long as it is a donor of hydrogen ions as Bronsted acid, but preferably tosyl acid, organic sulfonic acids such as camphor-sulfonic acid or hydrochloric acid, Mention may be made of inorganic acids such as sulfuric acid. The reaction temperature is 0 ° C to 150 ° C, preferably 80 ° C to 120 ° C.
The reaction time is usually 1 hour to 1 day, varying mainly depending on the reaction temperature, the raw material compound, the reaction reagent or the kind of the solvent used. The product is obtained as a mixture of geometric isomers, and each isomer can be separated by a conventional production means such as various chromatography and recrystallization.

[D method]

[0073]

[Chemical 13]

In the above formula, R ¹ , R ² , R ⁴ , X, Y,
A, m, n and p have the same meaning as described above.

[Method D] is a compound of the present invention in which R ³ and R ⁵ together represent the general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). CV) is a separate manufacturing method.

In the step D-1 , the compound (CII) is mixed with the aldehyde compound (DI), and the steps C-2 and C are carried out.
This is a step of producing a compound (DII) by reacting according to Step-3.

In the step D-2 , the compound (DII) and the compound (DII) having the general formula R ² -Y are used according to the Heck reaction.
I) and I) are reacted in the presence of a palladium salt such as palladium acetate or bis (triphenylphosphine) dichloropalladium in a solvent to produce the compound (CV) of the present invention. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, nitriles such as acetonitrile; aromatic such as benzene, toluene and xylene. Hydrocarbons; Esters such as ethyl acetate, propyl acetate; Ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane; Amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide or Mention may be made of sulfoxides such as dimethyl sulfoxide. The reaction temperature is 50 ° C to 200 ° C, preferably 80 ° C.
To 150 ° C. The reaction time is usually 8 hours to 2 days, varying mainly depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent used. The product is obtained as a mixture of geometrical isomers, and each isomer is obtained by a conventional production means such as various chromatography and recrystallization,
Can be separated.

[Method E]

[0079]

[Chemical 14]

In the above formula, R ¹ , R ² , R ⁴ , X, Y,
A, m, n and p have the same meaning as described above.

[Method E] is a compound of the present invention in which R ³ and R ⁵ are taken together to form the general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). CV) is a separate manufacturing method.

Step E-1 is a step of reacting compound (CI) with an active derivative of formic acid (EI) according to Step C-1 to produce a compound (EII) substituted with a nitrogen atom. is there.

In the step E-2 , the compound (E
II) and the ketone compound (CIII) are reacted according to the steps C-2 and C-3 to give the compound (EIII)
Is a step of manufacturing.

Step E-3 is for the compound (E
The formyl group of III) is removed according to the latter part of the step B-1 and then the compound (BI
This is a step of reacting with II) to produce the compound (CV) of the present invention.

[F method]

[0086]

[Chemical 15]

In the above formula, R ¹ , R ² , X, Y, m, n and p have the same meanings as described above.

[Method F] is a compound of the present invention in which R ³ and R ⁵ are taken together to form the general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). CV), a synthetic intermediate (E
This is a separate production method of III).

Step F-1 is the step of preparing the compound (E
II) and the aldehyde compound (DI) are reacted according to the above-mentioned step C-2 and step C-3 to give compound (FI)
Is a step of manufacturing.

In step F-2 , the compound (FI) synthesized above is reacted with the compound (DIII) having the general formula R ² -Y according to the Heck reaction to synthesize the compound (CV) of the present invention. A step of producing the body (EIII),
It is carried out according to two steps.

After completion of the reaction, the target compound of each reaction in each of the above steps is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding an organic solvent immiscible with water to the reaction mixture, washing with water and distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

R ³ and R ⁵ together form a compound of the general formula-(CH
₂ ) The carboxylic acid derivative (AI), which is a raw material compound of the compound of the present invention when _p − (wherein p is 1 to 3) is not produced, is produced as follows.

[G method]

[0094]

[Chemical 16]

In the above formula, R ¹ , R ² and R ³ have the same meanings as described above, R ⁷ represents the above "lower alkyl group",
R ⁸ represents the above “lower alkyl group” or the above “optionally substituted aryl group”.

The step G-1 is carried out by using a ketone compound (CII
I) and Horner's reagent (GI) [eg the well-known Arbuzov
It is produced by the reaction. ] In the presence of a base in a solvent to produce a compound (GII). The base used is not particularly limited as long as it is used as a base in a normal reaction, but preferably,
Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide, or 1,5-diazabicyclo [ 4.3.0] Non-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,
Mention may be made of organic bases such as 8-diazabicyclo [5.4.0] undec-7-ene (DBU) or organic metal bases such as butyllithium and lithium diisopropylamide. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene and xylene; ether. , Tetrahydrofuran, dioxane, dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide or sulfoxides such as dimethylsulfoxide.

In step G-2 , the protecting group R ⁷ for the carboxylic acid of compound (GII) is removed to give the starting compound (GI
This is a step of producing II). Removal of protecting groups is generally accomplished by treatment with acid or base by methods well known in the art. Hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid are used as the acid, and the base is not particularly limited as long as it does not affect the other parts of the compound, but sodium carbonate, carbonic acid are preferred. Alkali metal carbonates such as potassium; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide or concentrated ammonia-methanol. The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and water or water and methanol, ethanol.
Solvents such as alcohols such as alcohol and n-propanol or mixed solvents with organic solvents such as ethers such as tetrahydrofuran and dioxane are preferable. The reaction temperature and the reaction time vary depending on the starting material, the base used and the like and are not particularly limited.
It's time. The product is obtained as a mixture of geometrical isomers, and by using chromatography or the like according to a conventional method at each step of the G-1 step or G-2 step,
The (E) form and the (Z) form can each be isolated.

The starting compound (CIII) is, for example,
A compound having the formula R ¹ —CHO (wherein R ¹ has the same meaning as described above) and a compound having the formula R ² —MgZ (wherein
R ² has the same meaning as described above, and Z represents a halogen atom. )
Alternatively, it is reacted with a compound having the formula R ² -Li (wherein R ² has the same meaning as described above), or a compound having the formula R ² -C
A compound having HO (in the formula, R ² has the same meaning as described above) and a compound having the formula R ¹ -MgZ (in the formula, R ¹ and Z have the same meaning as described above) or the formula R ¹ It is produced by reacting with a compound having —Li (in the formula, R ¹ has the same meaning as described above), and then oxidizing the resulting alcohol compound to a carbonyl group according to a conventional method.

Utilizing the well-known Friedel-Crafts reaction, for example, a compound having the formula R ¹ -H (wherein R ¹ has the same meaning as described above) and a compound having the formula R ² -COZ ( Wherein R ² and Z have the same meanings as described above) or a compound having the formula R ² —H (wherein R ² has the same meanings as described above) and a formula R ¹ —COZ. Can also be produced by reacting a compound having the formula (wherein R ¹ and Z have the same meanings as described above).

[Method H]

[0101]

[Chemical 17]

In the above formula, R ¹ , R ² and R ⁷ have the same meanings as described above, and R ^{3 ′} represents a group other than a hydrogen atom in the definition of R ³ .

The first stage of the step H-1 is the compound (HI)
Is treated according to Step C-2, and then compound (C
This is a step of reacting with III) to produce the starting compound (HIII).

The second stage of the H-1 step is a step of treating the above-prepared compound (HIII) according to the C-3 step to produce the starting compound (HIV) of the present application.

In step H-2 , the compound (CIII) and the compound (HV) were activated in the presence of a solvent according to the method of Kamiya et al. (Pharmaceutical Journal, 88, 911 (1968)). Using a zinc dust, a reformatte-ski reaction was performed, and the obtained hydroxy ester was dehydrated and hydrolyzed in the same manner as in the step H-1 to obtain the starting compound (HI) of the present application.
This is a step of separately manufacturing V). In the previous process,
The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, hexane, heptane, ligroin, an aliphatic hydrocarbon such as petroleum ether or There may be mentioned aromatic hydrocarbons such as benzene, toluene and xylene,
Aromatic hydrocarbons are more preferred. Reaction temperature is 0
C. to boiling point, preferably 80.degree. C. to 10
It is 0 ° C. While the reaction time mainly varies depending on the reaction temperature, the raw material compound or the type of solvent used, it is generally 1 to 24 hours, and preferably 2 to 6 hours.

[Method I]

[0107]

[Chemical 18]

In the above formula, R ¹ , R ³ and R ⁷ have the same meanings as described above, and R ^{2 ′} represents the same group as the “group having the formula —R ⁶ ” in the definition of R ² .

In the step I-1 , the compound (II) and the compound having the formula R ^{2 ′} -Y (wherein R ^{2 ′} and Y have the same meanings as described above) are obtained by the Heck reaction. After the reaction according to the step D-2, the protecting group R ⁷ of the carboxylic acid is changed to the G-
This is a step of producing the starting compound (III) of the present application by removing it in accordance with two steps.

The starting compound (II) has the formula R ¹ -CHO
(Wherein R ¹ has the same meaning as described above)
Can be manufactured according to [G method] or [H method].

[Method J]

[0112]

[Chemical 19]

In the above formula, R ¹ , R ² , R ⁷ and Z are as defined above.

The step J-1 is a step for converting the compound (JI) to produce the starting compound (JII) of the present application.

[0115] R ² is to indicate R ^{2 ',} the compound (J
I) and a compound having the formula R ^{2 ′} -MgZ (wherein R ^{2 ′} and Z have the same meanings as described above) in a solvent, for example, bis (diphenylphosphino) ethanenickel (II) chloride After reacting in the presence of such a divalent nickel complex,
The protecting group R ⁷ of the carboxylic acid is removed according to the step G-2 to produce the starting compound (JII) of the present application. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably,
Mention may be made of aromatic hydrocarbons such as benzene, toluene, xylene or ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane.

When R ² represents a group other than R ^{2 '} , the compound (JI) and a compound having the formula R ⁶ -CH = CH ₂ (wherein
R ⁶ has the same meaning as described above. ) Or a compound having the formula R ⁶ -C ≡ CH (wherein R ⁶ has the same meaning as described above) in a solvent, for example, a palladium complex such as bis (triphenylphosphine) palladium (II) chloride. After the reaction is carried out in the presence of, the protecting group R ⁷ of the carboxylic acid is removed to produce the starting compound (JII) of the present application. In the reaction of the first stage, it may be preferable to carry out the reaction in the presence of an organic base such as triethylamine. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, Halogenated hydrocarbons such as chloroform; ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide or dimethylsulfoxide Mention may be made of sulfoxides.

The starting compound (JI) is obtained by adding a halogen atom such as chlorine or bromide to the compound (II) in which R ³ is a hydrogen atom, and then adding hydrogen chloride or hydrogen bromide. It can be produced by removing isohydrogen halide, forming a triple bond, and further adding hydrogen halide such as hydrogen bromide.

R ³ and R ⁵ together form a compound of the general formula-(CH
₂ ) The starting material compound (CI) of the compound of the present invention in the case where it represents _p − (wherein p represents 1 to 3) is produced, for example, as follows.

The starting compound (CI) for the compound of the present invention
Are mostly new compounds, but m = 1, n =
Compounds with 2 and p = 1 are described in WO 88/0313
No. 8 publication describes the structural formula. However, such a publication does not have a general manufacturing method and examples, and it is unknown whether or not it is actually manufactured, and it is impossible for a third party to repeat and synthesize it.

[K method]

[0121]

[Chemical 20]

In the above formula, X, m, n and p have the same meanings as described above, R ⁹ represents the above "lower alkyl group", and R
¹⁰ is, for example, tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-
Tetrahydropyranyl or tetrahydrothiopyranyl groups such as methoxytetrahydrothiopyran-4-yl; tetrahydrofuran-2-yl, tetrahydrothiofuran-2
A tetrahydrofuranyl or tetrahydrothiofuranyl group such as -yl; a tri-lower alkylsilyl group such as trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl A silyl group such as a tri-lower alkylsilyl group substituted with 1 to 2 aryl groups such as diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl and phenyldiisopropylsilyl; methoxymethyl, 1,1-dimethyl -1-Lower alkoxymethyl group such as methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-butoxymethyl, lower alkoxylated lower alkyl group such as 2-methoxyethoxymethyl Kishimechiru group, 2,
Alkoxymethyl groups such as halogeno lower alkoxymethyl such as 2,2-trichloroethoxymethyl and bis (2-chloroethoxy) methyl; lower alkoxylated ethyl groups such as 1-ethoxyethyl, 1- (isopropoxy) ethyl, 2,
Substituted ethyl groups such as halogenated ethyl groups such as 2,2-trichloroethyl; benzyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl Lower alkyl group substituted with 1 to 3 aryl groups such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl,
4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, methyl, lower alkyl such as piperonyl, lower alkoxy, halogen, cyano group Represents a hydroxyl-protecting group represented by an aralkyl group such as a lower alkyl group substituted with 1 to 3 aryl groups having a ring substituted, and can be preferably mentioned.
Preferably, it is a tetrahydropyranyl or tetrahydrothiopyranyl group.

In the K-1 step , for example, the carboxy group of a pyroglutamic acid or a pyro-2-aminoadipic acid derivative represented by the general formula (KI) is converted to a method described by Saijo et al.
m. Pharm. Bull., 5, 1449 (1980)] to produce an alcohol compound (KII).

The K-2 step is the Mitsunobu reaction [Synthesis, 19
81 , 1] to produce a compound (KIII) by reacting the compound (KII) with phthalimide in the presence of an azodicarboxylic acid ester such as diethyl azodicarboxylate and a trivalent phosphorus compound such as triphenylphosphine. It is a process to do. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene, xylene and diethyl ether. , Diisopropyl ether, tetrahydrofuran, dioxane and the like. Reaction temperature is 0
C. to 50.degree. C., preferably 10 to 3.degree.
It is 5 ° C. The reaction time is mainly the reaction temperature, the raw material compound,
Depending on the type of reaction reagent or solvent used,
It is usually 15 minutes to 1 day.

In Step K-3 , the compound (KIII) is replaced with
It is a step of reacting with compound (KIV) in a solvent in the presence of a base to alkylate a nitrogen atom to produce compound (KV). The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene and xylene; diethyl ether. , Diisopropyl ether, tetrahydrofuran, dioxane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide, or sulfoxides such as dimethyl sulfoxide and sulfolane. The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; Examples thereof include inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide, and organic metal bases such as butyllithium and lithium diisopropylamide. The reaction temperature is 0 ° C to 100 ° C, preferably room temperature. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of solvent used, but it is usually 1 to 24 hours.

In Step K-4 , the R ¹⁰ group and the phthaloyl group of the compound (KV) are removed in no particular order to give the compound (KV).
It is a process of manufacturing I). Removal of the R ¹⁰ group depends on its type, but is generally performed by methods well known in the art as follows.

When a silyl group is used as a hydroxyl-protecting group, it is usually removed by treatment with a compound which produces a fluorine anion such as tetrabutylammonium fluoride. The reaction solvent is not particularly limited as long as it does not inhibit the reaction, but ethers such as tetrahydrofuran and dioxane are preferable. Although the reaction temperature and the reaction time are not particularly limited, the reaction is usually performed at room temperature for 10 to 18 hours.

When the hydroxyl-protecting group is an aralkyl group, it is usually removed by bringing it into contact with a reducing agent in a solvent, preferably by catalytic reduction at room temperature under a catalyst for removal. A method or a method of removing using an oxidizing agent is preferable. The solvent used in the removal by catalytic reduction is not particularly limited as long as it does not participate in this reaction, but alcohols such as methanol, ethanol and isopropanol, diethyl ether, Tetrahydrofuran, ethers such as dioxane, toluene,
Of aromatic hydrocarbons such as benzene and xylene, aliphatic hydrocarbons such as hexane and cyclohexane, esters such as ethyl acetate and propyl acetate, fatty acids such as acetic acid or their organic solvent and water Mixed solvents are preferred. The catalyst used is not particularly limited as long as it is usually used in a catalytic reduction reaction, but is preferably palladium carbon, Raney-nickel, platinum oxide, platinum black, rhodium-aluminum oxide, trioxide. Phenylphosphine-rhodium chloride and palladium-barium sulfate are used. The pressure is not particularly limited, but is usually 1 to 10 atm. The reaction temperature and reaction time will differ depending on the types of starting materials and catalysts, but are usually 0 to 100 ° C.
For 5 minutes to 24 hours.

The solvent used for removal by oxidation is not particularly limited as long as it does not participate in this reaction, but a water-containing organic solvent is preferable. Preferable examples of such an organic solvent include ketones such as acetone, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, nitriles such as acetonitrile, diethyl ether, tetrahydrofuran, dioxane and the like. Ethers, amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide and sulfoxides such as dimethylsulfoxide. The oxidizing agent used is not particularly limited as long as it is a compound used for oxidation, but preferably potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3-dichloro- 5,6-Dicyano-p-benzoquinone (DDQ) is used. The reaction temperature and reaction time will differ depending on the types of starting materials and catalysts, etc., but are usually 0 to 150 ° C. and 10 minutes to 24 hours.

Further, in liquid ammonia or in methanol.
-78 in alcohols such as alcohol and ethanol
It can also be removed by reacting an alkali metal such as metallic lithium or metallic sodium at from -20 ° C.

Further, it can be removed by using aluminum chloride-sodium iodide or alkylsilyl halides such as trimethylsilyl iodide in a solvent. The solvent used is not particularly limited as long as it does not participate in the reaction, but preferably, nitriles such as acetonitrile, methylene chloride, halogenated hydrocarbons such as chloroform, or a mixed solvent thereof. Is used. The reaction temperature and the reaction time will differ depending on the starting materials and the like, but are usually 0 to 50 ° C., and 5 minutes to 3 days.

When the reaction substrate has a sulfur atom,
Aluminum chloride-sodium iodide is preferably used.

The hydroxyl-protecting group is an alkoxymethyl group,
When it is a tetrahydropyranyl group, a tetrahydrothiopyranyl group, a tetrahydrofuranyl group, a tetrahydrothiofuranyl group or a substituted ethyl group, it is usually added with water or a lower alcohol in a solvent in the presence of an acidic catalyst. It is removed by processing. The acidic catalyst used is not particularly limited as long as it is usually used as a Bronsted acid, and preferably an inorganic acid such as hydrochloric acid or sulfuric acid; an organic acid such as acetic acid or p-toluenesulfonic acid. Alternatively, those acid salts such as pyridine salt of p-toluenesulfonic acid, but strong acid cation exchange resins such as Dowex 50W can also be used. The solvent used is not particularly limited as long as it is an organic solvent which is not involved in this reaction and is miscible with water or a lower alcohol, but alcohols such as methanol and ethanol; dioxane,
Organic solvents such as acetone are preferred. The reaction temperature and reaction time will differ depending on the starting materials and the type of acid used, but they are usually 0 to 100 ° C. and 1 to 48 hours.

Removal of the phthaloyl group is achieved by treatment with a base in a solvent. The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably ammonia; hydrazine; organic bases such as methylamine, ethylamine and butylamine. You can The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably water; or methanol, ethanol, n-propanol, Isopropanol, n-butanol, isobutanol, t-butanol
Alcohol, alcohol such as isoamyl alcohol, or a mixed solvent thereof. Reaction temperature is 25 ° C to 120 ° C
However, the temperature is preferably 50 ° C. to 100 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of solvent used, but it is usually 1 to 48 hours.

In step K-6 , the compound (KVI) is treated under the conditions of the Mitsunobu reaction described in step K-2 and the ring is closed to produce the starting compound (CI) of the compound of the present invention. It is a process.

In addition, the compound (K
Since the (R) form and the '(S) form of I) can be synthesized from easily available glutamic acid or its homologue, 2-aminoadipic acid, the target compound (C
I) can also be produced as each optically active substance.

After completion of the reactions in the above steps, the target compound is
It is taken from the reaction mixture according to a conventional method. For example, it can be obtained by appropriately neutralizing the reaction mixture, or if insoluble matter is removed by filtration, adding an organic solvent immiscible with water, washing with water, and distilling off the solvent. If necessary, the obtained target compound is subjected to a conventional method such as recrystallization,
It can be further purified by reprecipitation or chromatography.

[0138]

【The invention's effect】

[0139]

Test Example 1 Inhibition of antihypertensive action by PAF As test animals, Wistar Imado rats (body weight 350-450 g) anesthetized with inactin (90 mg / kg ip) were used. Blood pressure was continuously measured from a cannula inserted into the femoral artery, and the drug was intravenously injected from a cannula inserted into the femoral vein. First, 10 ng / kg of C ₁₆ -PAF was intravenously injected at 5-minute intervals and repeated until the magnitude of the antihypertensive reaction became constant. Then, the test drug was intravenously injected, and 1 minute later, the same dose of PAF was administered again. The test drug was cumulatively administered, and the 50% inhibitory dose (ID ₅₀ ) was determined from the inhibitory rate of the PAF antihypertensive effect, which was used as an index of PAF antagonistic activity. PAF is 0.
A physiological saline solution containing 25% bovine serum albumin (BSA),
The test drug was dissolved in dimethylformamide before use. The results are shown below. ──────────────────────────────────── Test compound (Example number) Antihypertensive ID ₅₀ (mg) / kg) ──────────────────────────────────── 1 0.057 2 0.039 3 0.048 4 0.073 5 0.054 7 -1 0.014 7-2 0.058 7-9 0.022 7-10 0.074 7-11 0.0083 7-12 0.026 7-19 0.052 7-22 0.039 7-23 0.048 7-24 0.044 7-25 0.0067 7-27 0.0078 7-28 0.021 7-29 0.012 7-30 0.039 7-33 0.0080 7-35 0.0071 7-36 0.0050 7-37 0.0044 7-38 0.0075 7-39 0.0066 7-42 0.012 7-43 0.0080 7-46 0.0084 7-47 0.0074 7 -50 0.011 7-51 0.0033 7-52 0.0074 7-53 0.0097 7-54 0.0084 7-55 0.0055 7-56 0.0051 7-57 0.0092 7-58 0.0037 7 59 0.0073 7-61 0.0066 7-64 0.0065 7-66 0.013 7-68 0.011 7-69 0.0086 7-70 0.0061 7-71 0.015 22 0.011 23 0.092 25 0.028 28 0.049 29 0.071 30 0.062 Target compound (CV-3988) 0.42 ────────────────────────────────────

[0140]

[Test Example 2] Inhibitory effect of PAF platelet aggregation in vitro Blood was collected from rabbits and immediately mixed with 1/9 volume of 3.8% sodium citrate. After centrifugation at 150 g for 15 minutes at room temperature, platelet rich plasma (PRP) was obtained from the upper layer. The remaining blood was centrifuged at 1000 g for an additional 15 minutes, and platelet poor plasma (PP
P) was obtained. PRP and PPP were mixed in an appropriate amount, and the final platelet count of PRP was adjusted to 600,000 per μl. Platelet aggregation was performed by the method of Bourne et al. (GVR Born, J. Physiol., 62, 67-
68 (1962)) using an aglycometer to measure the increase in transmitted light. To 272 μl of PRP, add 3 μl of the test drug in dimethyl sulfoxide, and after 1 minute, add 25 μl of C
_16- PAF physiological saline solution (final concentration 10 ^{−8 to} 3 × 10 ⁻⁸ M) was added, and then observed for 5 minutes to confirm the aggregation suppressing action. The inhibition rate was determined based on the aggregation by PAF when dimethyl sulfoxide was used instead of the test solution, and was determined by a dose-response curve.
It was calculated the IC _50. The results are shown below. ──────────────────────────────────── Test compound (Example number) Platelet aggregation inhibition IC ₅₀ (M ) ──────────────────────────────────── 1 3.2 × 10 ^-7 2 2.0 × 10 ^-7 3 ^{2.2 × 10 -7 5 2.6 × 10} -7 7-1 2.8 × 10 -7 7-9 6.8 × 10 -8 7-11 6.3 × 10 -8 7-22 2.3 × 10 -7 7-23 1.8 × 10 - ⁷ 7-24 1.5 × 10 ^-7 7-25 4.4 × 10 ^-8 7-27 4.3 × 10 ^-8 7-29 1.1 × 10 ^-7 7-30 2.2 × 10 ^-7 7-31 1.1 × 10 ^-7 7 -34 1.1 × 10 ^-7 7-35 6.7 × 10 ^-8 7-39 3.9 × 10 ^-8 7-43 6.6 × 10 ^-8 7-46 3.0 × 10 ^-8 7-47 5.2 × 10 ^-8 7-51 3.0 x 10 ^-8 7-52 3.8 x 10 ^-8 7-54 8.6 x 10 ^-8 7-55 5.8 x 10 ^-8 7-56 9.9 x 10 ^-8 7-57 8.3 x 10 ^-8 7-58 2.6 x ^{10 -8 7-59 2.9 × 10 -8 7-64} 2.8 × 10 -8 7 ^{65 3.1 × 10 -8 7-66 9.9 ×} 10 -9 22 6.5 × 10 -8 25 3.0 × 10 -8 27 7.5 × 10 -9 control compounds (CV-3988) 9.8 × 10 -6 ────── ──────────────────────────────

[0141]

[Test Example 3] Inhibitory effect of PAF receptor binding Heart blood was collected from a rabbit and immediately 1/9 volume of 0.77 M EDTA.
2 Mixed with sodium solution. A platelet precipitate was obtained in the same manner as in Test Example 2. The washed platelets were repeatedly frozen and thawed to destroy them, and then overlaid on top of two sucrose liquid layers of 0.25 M and 1.5 M. This is 4 ℃, 6
After centrifugation at 3,500 xg for 2 hours, the fraction collected at the interface between 0.25 M and 1.5 M sucrose was used as the PAF receptor membrane fraction. The receptor binding experiment was carried out by the method of Huang et al.
al., J. Biol. Chem., 260 , 15639-15645 (1985)), the specific binding amount of ³ H-PAF was measured by Whatman.
It measured using the GF / C filter. The compound was dissolved in dimethylsulfoxide, diluted 100-fold with a buffer containing 0.5% bovine serum albumin, and mixed so as to be 1/10 volume of the reaction solution for receptor binding experiment. The binding inhibition rate (%) was plotted against the log of the compound concentration, and the 50% inhibition concentration (IC ₅₀ ) was determined from the straight line connecting the points. The results are shown below. ──────────────────────────────────── Test compound (Example number) Receptor binding inhibition IC ₅₀ ( M) ──────────────────────────────────── 1 4.7 × 10 ^-8 5 4.7 × 10 ^-8 7-9 4.3 × 10 ^-8 7-25 1.4 × 10 ^-8 7-35 1.7 × 10 ^-7 7-36 2.0 × 10 ^-8 7-37 1.3 × 10 ^-8 7-38 1.5 × 10 ^-8 7- 39 1.6 × 10 ^-8 7-43 2.1 × 10 ^-8 7-50 3.5 × 10 ^-8 7-53 2.6 × 10 ^-8 7-56 2.3 × 10 ^-8 7-58 1.4 × 10 ^-8 7-65 3.2 × 10 ^-8 7-68 1.4 × 10 ^-8 7-69 4.0 × 10 ^-8 7-70 2.0 × 10 ^-8 22 7.6 × 10 ^-8 27 2.0 × 10 ^-8 29 5.6 × 10 ^-8 30 6.0 × 10 ^-8 Control compound (CV-3988) 1.6 × 10 ^-6 ─────────────────────────────────────

[0142]

[Test Example 4] Acute toxicity test Example 2 was performed on male ddY mice (5 weeks old, 3 mice in each group).
Oral administration of compound 7-1 or 7-9 (dose 300 mg / kg
)did. After one week, no deaths were observed in any of the administration groups.

As described above, the novel N- (3,
The 3-di-substituted acryloyl) piperazine derivative has excellent PAF antagonism and is not toxic, so various diseases thought to involve PAF, such as endotoxin shock, anaphylactic shock, nephritis, myocardial infarction. , Is useful as a therapeutic agent for angina, asthma, psoriasis, gastric ulcer and the like.

The administration form of the compound (I) of the present invention is as follows:
For example, oral administration by tablets, capsules, granules, powders, syrups and the like or parenteral administration by injections, suppositories and the like can be mentioned. These formulations are
It is manufactured by a well-known method using additives such as an excipient, a binder, a disintegrant, a lubricant, a stabilizer, and a flavoring agent. The dose varies depending on symptoms, age, etc., but 0.001-100 mg / k / day
The g body weight, preferably 0.2 to 50 mg / kg body weight per day, can be administered to an ordinary adult once a day or in several divided doses.

The present invention will be described more specifically below with reference to Examples, Reference Examples and Production Examples.

[0146]

Example 1 1- (3-phenylcinnamoyl) -4- (3,4,5-trimethoxy
Benzoyl) piperazine 3-phenylcinnamic acid (4.485 g) in methylene chloride (90 ml)
The solution was cooled to 0-5 ° C and phosphorus pentachloride (4.164 g) was added. The reaction solution was stirred at room temperature for 1 hour, and the solvent was evaporated. The residue was dissolved in toluene (50 ml), and the solvent was distilled off again. The same operation was repeated once more to give 3-phenylcinnamic acid chloride as a white solid. This crude product was immediately used in the following reaction. 1- (3,4,5-trimethoxybenzoyl) piperazine (1.401
To a solution of g) in tetrahydrofuran (30 ml) was added sodium hydrogencarbonate (0.840 g) dissolved in water (15 ml). In this mixture was added 3-phenylcinnamic acid chloride (1.214
g) was added at once and stirred for 30 minutes at room temperature. Methylene chloride (50 ml) was added to the reaction solution to separate the layers, and the aqueous layer was extracted with methylene chloride. Combine the methylene chloride layers,
It was washed successively with 10% hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated saline. After drying over sodium sulfate, the solvent was evaporated and the oily residue (2.70 g) was subjected to silica gel flash chromatography. Collect the fractions eluted with methylene chloride-methanol (100: 1) and
(2.150 g) was obtained as a white powder. Recrystallization from ethyl acetate-hexane gave white needle crystals (melting point: 148-150 ° C). NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.65-3.80 (8
H, m); 3.84 (6H, s); 3.85 (3H, s); 6.30 (1H, s); 6.52 (2H,
s); 7.2-7.5 (10H, m ) Mass spectrum (m / z):. 486 (M +); 291 (M + -C 10 H 11 O 4); 27
9 (M ⁺ -C ₁₅ H ₁₁ O); 207 (C ₁₅ H ₁₁ O); 195 (C ₁₀ H ₁₁ O ₄ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 158
5. Elemental analysis (as C ₂₉ H ₃₀ N ₂ O ₅ ) Calculated: C; 71.59, H; 6.21, N; 5.76. Found: C; 71.54, H; 6.44, N; 5.71.

[0147]

Example 2 1- [3,3-bis (4-methoxyphenyl) acryloyl] -4-
(3,4,5-Trimethoxybenzoyl) piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (0.500 g)
Thus, in the same manner as in Example 1, the title compound (0.362 g)
Was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.75 (8
H, m); 3.82 (3H, s); 3.84 (3H, s); 3.85 (9H, s); 6.14 (1H,
s); 6.54 (2H, s); 6.80-6.93 (4H, m); 7.18-7.30 (4H, m). Mass spectrum (m / z): 546 (M ⁺ ); 351 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 27
^{_{9 (M + -C 17 H 15}} O 3); 267 (C 1 7 H 15 O 3); 195 (C 10 H 11 O 4) Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1:. 1625, 160
5, 1585.

[0148]

Example 3 1- [3,3-bis (4-chlorophenyl) acryloyl] -4-
(3,4,5-Trimethoxybenzoyl) piperazine 3,3-bis (4-chlorophenyl) acrylic acid (0.500 g) was used to obtain the title compound (0.938 g) as a white powder in the same manner as in Example 1. It was NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.70 (8
H, m); 3.86 (9H, s); 6.32 (1H, s); 6.56 (2H, s); 7.15-7.4
0 (8H, m). Mass spectrum (m / z): 554 (M ⁺ ); 359 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 27
9 (M ⁺ -C ₁₅ H ₉ Cl ₂ O); 275 (C ₁₅ H ₉ Cl ₂ O); 195 (C ₁₀ H ₁₁ O ₄ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630 , 159
0.

[0149]

Example 4 1- [3,3-bis (2-thienyl) acryloyl] -4- (3,4,5-
Trimethoxybenzoyl) piperazine 3,3-bis (2-thienyl) acrylic acid (0.500 g) was obtained in the same manner as in Example 1 to obtain the title compound (0.719 g) as a white powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.75 (8
H, m); 3.85 (9H, s); 6.34 (1H, s); 6.57 (2H, s); 7.02 (1H,
dd, J = 5.13,3.66Hz); 7.08 (1H, dd, J = 5.13,3.66Hz); 7.13
(1H, dd, J = 1.10,3.66Hz); 7.26 (1H, dd, J = 1.10,3.66Hz);
7.32 (1H, dd, J = 5.13,1.10Hz); 7.42 (1H, dd, J = 5.13,1.10H
z). Mass spectrum (m / z): 498 (M ⁺ ); 30
3 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 279 (M ⁺ -C
₁₁ H ₇ OS ₂ ); 219 (C _{1 1} H ₇ OS ₂ );
_{195 (C 10 H 11 O 4} ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1620, 15
85. Elemental analysis (as C ₂₅ H ₂₆ N ₂ O ₅ S ₂ ) Calculated: C; 60.22, H; 5.26, N; 5.62, S; 12.86. Found: C; 60.34, H; 5.43, N; 5.59, S; 12.97.

[0150]

Example 5 1- [Z-3-phenyl-3- (2-thienyl) acryloyl] -4-
(3,4,5-Trimethoxybenzoyl) piperazine From Z-3-phenyl-3- (2-thienyl) acrylic acid (melting point: 144 to 147 ° C., 0.480 g) obtained in Reference Example 1, 1
In the same manner as in the above, the title compound (0.703 g) was obtained as a white powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.75 (8
H, m); 3.84 (3H, s); 3.85 (6H, s); 6.41 (1H, s); 6.53 (2H,
s); 6.88 (1H, dd, J = 3.67,1.10Hz); 6.98 (1H, dd, J = 5.13,
3.67Hz); 7.30 (1H, dd, J = 5.13,1.10Hz); 7.40 (5H, s-lik
e). Mass spectrum (m / z): 492 (M ⁺ ); 297 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 27
9 (M ⁺ -C ₁₃ H ₉ OS); 213 (C ₁₃ H ₉ OS); 195 (C ₁₀ H ₁₁ O ₄ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1620, 158
5. Elemental analysis value (as C ₂₇ H ₂₈ N ₂ O ₅ S) Calculated value: C; 65.83, H; 5.73, N; 5.69, S; 6.51. Measured value: C; 65.68, H; 5.97, N; 5.79 , S; 6.51.

[0151]

Example 6 1- [E-3-phenyl-3- (4-pyridyl) acryloyl] -4-
(3,4,5-Trimethoxybenzoyl) piperazine Obtained in Reference Example 3, E-3-phenyl-3- (4-pyridyl) acrylic acid (melting point: 239 to 241 ° C, 0.224 g) and triethylamine (0.28 ml) in methylene chloride (5 ml), diphenylphosphoric acid azide (0.330 g) in methylene chloride (1 ml)
Solution and 1- (3,4,5-trimethoxybenzoyl) piperazine
(0.280 g) was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with methylene chloride (20 ml) and washed with 5% aqueous sodium hydrogen carbonate solution and saturated brine. The organic layer was dried over sodium sulfate, the solvent was distilled off, and 0.686 g of the oily residue was subjected to silica gel flash column chromatography. Fractions eluted with methylene chloride-methanol (100: 2-100: 3) were collected to give the title compound (0.419 g) as a white powder. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 3.05-3.70 (8H,
m); 3.84 (9H, m); 6.50 (1H, s); 6.58 (2H, s); 7.10-7.68
(7H, m); 8.45-8.85 (2H, m). Mass spectrum (m / z): 487 (M ⁺ ); 292 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 27
^{_{9 (M + -C 14 H 10}} NO); 208 (C 1 4 H 10 NO); 195 (C 10 H 11 O 4) Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1:. 1630.

[0152]

Example 7 N- (3,3, -bis-substituted phenyl) acryloyl-N- (3,4,5-to)
Synthesis of Limethoxybenzoyl ) -piperazine Derivatives The following compounds 7-1 to 7-72 were prepared according to the general method described below in Reference Examples 4-1 to 4-174, 11, 14 and 15
Was synthesized from the compound.

[ General Synthesis Method ] 3,3-Disubstituted acrylic acid derivative (Reference Examples 4-1 to 4-174, 11, 14 and 1)
5) 1.60 mmol and triethylamine 0.67 ml (4.80 mmol)
Diphenylphosphoric acid azide (0.793 g, 2.88 mmol) and N- (3,4,5-trimethoxybenzoyl) piperazine (0.449 g, 1.60 mmol) were sequentially added to the methylene chloride (7 ml) solution of. The reaction mixture was stirred at room temperature for 3 hours and then diluted with methylene chloride (20 ml). This solution was washed successively with saturated aqueous sodium hydrogen carbonate solution, 10% hydrochloric acid and water, dried and the solvent was distilled off. The residue was subjected to medium pressure liquid chromatography using two Roper B columns connected in series. Elution with ethyl acetate removed less polar impurities, followed by methylene chloride-methanol (100: 1-1
(00: 2) elutes the desired N- (3,3-disubstituted acryloyl) -N- (3,4,5-trimethoxybenzoyl) piperazine derivative in 50-99% yield. It was When these compounds were amorphous solids, they were crushed and dried, and when they were obtained as crystals, they were recrystallized from an appropriate solvent to prepare samples for biological tests.

[0154]

[Chemical 21]

[0155]

Example 7-1 Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, Configuration = E Raw material (reference example number) = 4-3. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.70-3.70 (8
H, m), 3.81 (3H, s), 3.84 (9H, s), 3.90 (3H, s), 6.25 (1H,
s), 6.52 (2H, s), 6.76-6.88 (3H, m), 7.27-7.42 (5H, m). Mass spectrum (m / z): 546 (M ⁺ ), 351; 279; 267; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1515, 1460, 1420, 1330, 1130.

[0156]

Example 7-2 Compound with R ¹ = Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw material (reference example number) = 4-4. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.22 (1H,
s), 6.55 (2H, s), 6.80 (1H, dd, J = 8.30,1.46Hz), 6.86 (1
H, d, J = 8.30Hz), 6.86-6.88 (1H, m), 7.28-7.40 (5H, m). Mass spectrum (m / z): 546 (M ⁺ ), 351; 279; 267; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 158
5, 1515, 1460, 1420, 1335, 1130.

[0157]

Example 7-3 Compound with R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, Configuration = E Raw material (reference example number) = 4-7. Yield (%) = 74. Melting point (recrystallization solvent) = 166-168 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.70-3.70 (8
H, m), 3.78 (3H, s), 3.846 (9H, s), 3.850 (3H, s), 3.87 (3
H, s), 6.26 (1H, s), 6.47 (2H, s), 6.53 (2H, s), 7.28-7.4
2 (5H, m). Mass spectrum (m / z): 576 (M ⁺ ), 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1505, 1460, 1415, 1330, 1125.

[0158]

Example 7-4 Compound with R ¹ = Ph, R ² = 3,4,5-tri-CH ₃ OPh, Configuration = Z Raw material (reference example number) = 4-8. Yield (%) = 79. Melting point (recrystallization solvent) = 149-151 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.80-3.70 (8
H, m), 3.77 (6H, s), 3.85 (3H, s), 3.86 (6H, s), 3.89 (3H,
s), 6.25 (1H, s), 6.53 (2H, s), 6.54 (2H, s), 7.28-7.40
(5H, m). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 1585,
1505, 1460, 1415, 1335, 1125.

[0159]

Example 7-5 Compound with R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, Configuration = E Raw material (reference example number) = 4-11. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (3H, t, J =
7.32Hz), 1.88 (2H, m), 2.70-3.65 (8H, m), 3.79 (3H, s),
3.84 (6H, s), 3.85 (3H, s), 3.99 (2H, t, J = 6.83Hz), 6.24 (1
H, s), 6.53 (2H, s), 6.75-6.85 (3H, m), 7.27-7.43 (5H,
m). Mass spectrum (m / z): 574 (M ⁺ ); 531; 379; 295; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0160]

Example 7-6 Compound in which R ¹ = Ph, R ² = 3-CH ₃ O-4-PrO-Ph and configuration = Z Raw material (reference example number) = 4-12. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.32Hz), 1.89 (2H, m), 2.80-3.70 (8H, m), 3.78 (3H, s),
3.85 (3H, s), 3.86 (6H, s), 4.00 (3H, t, J = 6.84Hz), 6.20 (1
H, s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.30,1.46Hz), 6.85-
6.95 (2H, m), 7.27-7.40 (5H, m). Mass spectrum (m / z): 574 (M ⁺ ); 531; 379; 295; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1630, 1600, 1590, 151
5, 1465, 1420, 1335, 113
0.

[0161]

Example 7-7 Compound with R ¹ = 3,4-di-PrOPh, R ² = Ph, Configuration = E Raw material (reference example number) = 4-15. Yield (%) = 87. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.33Hz), 1.05 (3H, t, J = 7.33Hz), 1.85 (4H, m), 2.70-3.7
0 (8H, m), 3.84 (6H, s), 3.85 (3H, s), 3.88 (2H, t, J = 6.83H
z), 3.97 (2H, t, J = 6.84Hz), 6.23 (1H, s), 6.53 (2H, s),
6.80 (3H, s), 7.25-7.40 (5H, m). Mass spectrum (m / z): 602 (M ⁺ ); 559; 517; 407; 323;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0162]

Examples 7-8 Compounds with R ¹ = Ph, R ² = 3,4-di-PrOPh, configuration = Z Raw material (reference example number) = 4-16. Yield (%) = 88. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.32Hz), 1.06 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 2.7
0-3.70 (8H, m), 3.85 (9H, s), 3.85-3.92 (2H, m), 3.99 (2
H, t, J = 6.84Hz), 6.19 (1H, m), 6.55 (2H, s), 6.75-6.90 (3
H, m), 7.28-7.40 (5H, m). Mass spectrum (m / z): 602 (M ⁺ ); 559; 517; 407; 323;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0163]

Example 7-9 Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-Cl-Ph, Configuration = E Raw material (reference example number) = 4-19. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 3.90 (3H, s), 6.28 (1H,
s), 6.56 (2H, s), 6.75 (1H, br.s), 6.81 (2H, br.s), 7.20-
7.38 (4H, m, AB type). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1510, 1460, 1420, 1330, 1130.

[0164]

[Examples 7-10] Compounds in which R ¹ = 4-ClPh, R ² = 3,4-di-CH ₃ OPh and configuration = Z Raw material (reference example number) = 4-20. Yield (%) = 71. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.80 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.20 (1H,
s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.25,1.95Hz), 6.86 (1
H, d, J = 8.25Hz), 6.81-6.87 (1H, m), 7.20-7.36 (4H, m, AB
Type) .Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1635, 159
5, 1515, 1465, 1425, 1335, 1135.

[0165]

[Examples 7-11] Compounds in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, and configuration = Z Raw material (reference example number) = 4-23. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 3.90 (3H, s), 6.29 (1H,
s), 6.57 (2H, s), 6.77 (1H, br.s), 6.82 (2H, m), 7.15-7.
43 (4H, m). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1515, 1460, 1420, 1330, 1130.

[0166]

Examples 7-12 Compounds with R ¹ = 3-ClPh, R ² = 3,4-di-CH ₃ OPh, Configuration = E Raw material (reference example number) = 4-24. Yield (%) = 90. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.22 (1H,
s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.30,1.95Hz), 6.85 (1
H, m), 6.87 (1H, d, J = 8.30Hz), 7.13-7.38 (4H, m). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1515, 1460, 1420, 1330, 1260, 1130.

[0167]

[Examples 7-13] Compounds in which R ¹ = 2,3-di-CH ₃ OPh, R ² = 4-ClPh, and configuration = E Raw material (reference example number) = 4-27. Yield (%) = 85. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.57 (3H, s), 3.86 (9H, s), 3.87 (3H, s), 6.17 (1H,
s), 6.55 (2H, s), 6.75 (1H, dd, J = 7.81,1.46Hz), 6.93 (1
H, dd, J = 8.30,1.46Hz), 7.04 (1H, t, J = 8.30Hz), 7.25 (2H,
dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 549; 301; 195. Infrared absorption spectrum ν _max ( CHCl ₃ ) cm
-1: 1635, 1595, 1470, 143
0, 1335, 1135.

[0168]

[Examples 7-14] Compounds in which R ¹ = 4-ClPh, R ² = 2,3-di-CH ₃ OPh and configuration = Z Raw material (reference example number) = 4-28. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.855 (9H, s), 3.859 (6H, s), 6.38 (1H, s), 6.57 (2
H, s), 6.86 (1H, dd, J = 8.30,1.47Hz), 6.96 (1H, dd, J = 8.3
0,1.47Hz), 7.07 (1H, t, J = 8.30Hz), 7.20 (2H, dm, J = 8.79H
z), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 549; 301; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1630, 158
5, 1460, 1420, 1330, 1125.

[0169]

Example 7-15 Compound with R ¹ = 4-i-BuOPh, R ² = 4-ClPh, Configuration = Z Raw material (reference example number) = 4-31. Yield (%) = 75. Melting point (recrystallization solvent) = 122-124 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (6H, d, J =
6.83Hz), 2.09 (1H, m), 2.80-3.65 (8H, m), 3.73 (2H, d, J =
6.34Hz), 3.86 (9H, s), 6.26 (1H, s), 6.56 (2H, s), 6.84 (2
H, dm, J = 8.30Hz), 7.17 (2H, dm, J = 8.30Hz), 7.22 (2H, dm, J
= 8.30Hz), 7.34 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 592 (M ⁺ , ³⁵ Cl); 535; 397; 313;
279; 257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1590, 1510, 1460, 1425, 1330, 1175, 1130.

[0170]

Examples 7-16 Compounds with R ¹ = 4-ClPh, R ² = 4-i-BuOPh, Configuration = E Raw material (reference example number) = 4-32. Yield (%) = 59. Melting point (recrystallization solvent) = 128-129 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (6H, d, J =
6.84Hz), 2.10 (1H, m), 2.70-3.65 (8H, m), 3.75 (2H, d, J =
6.35Hz), 3.84 (6H, s), 3.85 (3H, s), 6.18 (1H, s), 6.54 (2
H, s), 6.88 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz),
7.21 (2H, dm, J = 8.30Hz), 7.30 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 592 (M ⁺ , ³⁵ Cl); 535; 397; 313;
279; 257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1490, 1460, 1425, 1330, 1285, 1175,
1130.

[0171]

Example 7-17 Compound with R ¹ = 4-PrOPh, R ² = 4-ClPh, Configuration = Z Raw material (reference example number) = 4-35. Yield (%) = 76. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 2.80-3.65 (8H, m), 3.86 (9
H, s), 3.93 (2H, t, J = 6.84Hz), 6.26 (1H, s), 6.56 (2H, s),
6.85 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz), 7.22
(2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 535; 383; 299;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1425, 1330, 1130.

[0172]

Examples 7-18 Compounds with R ¹ = 4-ClPh, R ² = 4-PrOPh, Configuration = E Raw material (reference example number) = 4-36. Yield (%) = 74. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.75-1.92 (2H, m), 2.80-3.70 (8H, m), 3.846 (6
H, s), 3.850 (3H, s), 6.18 (1H, s), 6.54 (2H, s), 6.88 (2
H, dm, J = 8.78Hz), 7.17 (2H, dm, J = 8.78Hz), 7.24 (2H, dm, J
= 8.30Hz), 7.30 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 535; 383; 299;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1130.

[0173]

Example 7-19 Compound of R ¹ = 4-FPh and R ² = 4-FPh Raw material = 3,3-bis (4-fluorophenyl) acrylic acid (known compound). Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.70-3.70 (8
H, m), 3.85 (9H, s), 6.27 (1H, s), 6.56 (2H, s), 6.97-7.1
3 (4H, m), 7.20-7.33 (4H, m). Mass spectrum (m / z): 522 (M ⁺ ); 327; 327; 279; 243; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1630, 160
0, 1585, 1505, 1460, 1420, 1330, 1125.

[0174]

[Examples 7-20] Compounds in which R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, and configuration = E Raw material (reference example number) = 4-39. Yield (%) = 77. Melting point (recrystallization solvent) = 195-197 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.80-3.70 (8
H, m), 3.79 (6H, s), 3.86 (9H, s), 3.87 (3H, s), 6.27 (1H,
s), 6.45 (2H, s), 6.56 (2H, s), 7.05-7.13 (2H, m), 7.25-
7.33 (2H, m). Mass spectrum (m / z): 594 (M ⁺ ); 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1505, 1460, 1415, 1330, 1125.

[0175]

Example 7-21 Compound with R ¹ = 4-FPh, R ² = 3,4,5-tri-CH ₃ OPh, Configuration = Z Raw material (reference example number) = 4-40. Yield (%) = 78. Melting point (recrystallization solvent) = 130-132 ° C (CH ₂ Cl ₂ -Et ₂ O) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.80-3.70 (8
H, m), 3.77 (6H, s), 3.85 (3H, s), 3.86 (6H, s), 3.89 (3H,
s), 6.20 (1H, s), 6.51 (2H, s), 6.54 (2H, s), 7.00-7.09
(2H, m), 7.26-7.35 (2H, m). Mass spectrum (m / z): 594 (M ⁺ ); 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625 , 160
0, 1585, 1505, 1460, 1415, 1125.

[0176]

Example 7-22 Compound of R ¹ = 3,4-di-CH ₃ OPh and R ² = 3,4-di-CH ₃ OPh Raw material = 3,3-bis (3,4-dimethoxyphenyl) acryl Acid (known compound). Yield (%) = 74. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.82 (3H, s), 3.86 (9H, s), 3.91 (3H,
s), 3.92 (3H, s), 6.16 (1H, s), 6.56 (2H, s), 6.80-6.95
(6H, m). Mass spectrum (m / z): 606 (M ⁺ ); 411; 327; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1515, 1460, 1420, 1330, 1250, 1125.

[0177]

[Example 7-23] Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, configuration = E Raw material (reference example number) = 4-43. Yield (%) = 54. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.85 (12H, s), 3.90 (3H, s), 6.16 (1
H, s), 6.55 (2H, s), 6.76-6.85 (3H, m), 6.89 (2H, dm, J = 8.
78Hz), 7.22 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625 , 160
0, 1585, 1510, 1460, 1420, 1330, 1130.

[0178]

[Examples 7-24] Compounds in which R ¹ = 4-CH ₃ OPh, R ² = 3,4-di-CH ₃ OPh and configuration = Z Raw material (reference example number) = 4-44. Yield (%) = 73. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.80 (3H, s), 3.83 (3H, s), 3.86 (9H, s), 3.92 (3H,
s), 6.15 (1H, s), 6.55 (2H, s), 6.78-6.91 (5H, m), 7.12-
7.26 (2H, m). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1585, 1510, 1460, 1420, 1330, 1130.

[0179]

Example 7-25 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-47. Yield (%) = 85. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.10-3.70 (8
H, m), 3.83 (3H, s), 3.857 (3H, s), 3.861 (6H, s), 6.32 (1
H, s), 6.58 (2H, s), 6.87 (2H, dm, J = 8.79Hz), 7.13 (1H, d
d, J = 8.30,1.95Hz), 7.18 (2H, dm, J = 8.79Hz), 7.36 (1H, d,
J = 1.95Hz), 7.45 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1125.

[0180]

Example 7-26 Compound with R ¹ = 3,4-di-ClPh, R ² = 4-CH ₃ OPh, Configuration = E Raw material (reference example number) = 4-48. Yield (%) = 84. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (12H, s), 6.21 (1H, s), 6.54 (2H, s), 6.90 (2
H, dm, J = 8.79Hz), 7.10 (1H, dd, J = 8.30,1.95Hz), 7.18 (2
H, dm, J = 8.79Hz), 7.38 (1H, d, J = 1.95Hz), 7.40 (1H, d, J =
Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1130.

[0181]

[Example 7-27] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CF ₃ Ph and configuration = E Raw material (reference example number) = 4-51. Yield (%) = 74. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.82 (3H, s), 3.848 (6H, s), 3.853 (3H, s), 3.91 (3
H, s), 6.37 (1H, s), 6.56 (2H, s), 6.77 (1H, br.s), 6.79-
6.88 (2H, m), 7.47-7.60 (3H, m), 7.60-7.71 (1H, m). Mass spectrum (m / z): 614 (M ⁺ ); 419; 335; 307; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1625, 1600, 1585, 151
0, 1460, 1420, 1325, 130
0, 1170, 1125.

[0182]

[Example 7-28] Compound having R ¹ = 3-CF ₃ Ph, R ² = 3,4-di-CH ₃ OPh and configuration = Z Raw material (reference example number) = 4-52. Yield (%) = 50. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.85 (3H, s), 3.86 (6H, s), 3.93 (3H,
s), 6.26 (1H, s), 6.56 (2H, s), 6.78 (1H, dd, J = 8.30,1.96
Hz), 6.86 (1H, m), 6.87 (1H, d, J = 8.30Hz), 7.43-7.53 (2
H, m), 7.53-7.67 (2H, m). Mass spectrum (m / z): 614 (M ⁺ ); 419; 335; 307; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1515, 1460, 1420, 1325, 1255, 1165, 1125.

[0183]

[Example 7-29] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, configuration = E Raw material (reference example number) = 4-55. Yield (%) = 89. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.39 (3H, s),
2.80-3.70 (8H, m), 3.81 (3H, s), 3.848 (6H, s), 3.851 (3
H, s), 3.89 (3H, s), 6.20 (1H, s), 6.54 (2H, s), 6.79 (1H,
br.s), 6.80-6.90 (2H, m), 7.17 (4H, s). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max ( CHCl ₃ ) cm-1: 1620, 160
0, 1585, 1510, 1460, 1420, 1330, 1125.

[0184]

Example 7-30 Compound with R ¹ = 4-CH ₃ Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw material (reference example number) = 4-56. Yield (%) = 99. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.37 (3H, s),
2.80-3.70 (8H, m), 3.80 (3H, s), 3.85 (3H, s), 3.86 (6H,
s), 3.91 (3H, s), 6.19 (1H, s), 6.55 (2H, s), 6.80 (1H, d
d, J = 8.30,1.46Hz), 6.84 (1H, m), 6.85 (1H, d, J = 8.30Hz),
7.14 (2H, d, J = 8.30Hz), 7.19 (2H, d, J = 8.30Hz). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1510, 1460, 1420, 1330, 1255, 1125.

[0185]

Example 7-31 Compound with R ¹ = 3-CH ₃ Ph, R ² = 3,4-di-ClPh, Configuration = Z Raw material (reference example number) = 4-59. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.90-3.70 (8H, m), 3.857 (3H, s), 3.862 (6H, s), 6.36 (1
H, s), 6.58 (2H, s), 7.00-7.07 (2H, m), 7.13 (1H, dd, J = 8.
30Hz), 7.16-7.28 (2H, m), 7.36 (1H, d, J = 1.96Hz), 7.45
. (1H, d, J = 8.30Hz) Mass spectrum (m / z): 568 ( M +, 35 Cl); 373; 289; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1635, 159
0, 1465, 1425, 1335, 1130.

[0186]

[Example 7-32] Compound in which R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, and configuration = E Raw material (reference example number) = 4-60. Yield (%) = 92. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.35 (3H, s),
2.70-3.70 (8H, m), 3.84 (6H, s), 3.85 (3H, s), 6.27 (1H,
s), 6.53 (2H, s), 7.02-7.14 (3H, m), 7.18-7.32 (2H, m),
7.36-7.44 (3H, m). Mass spectrum (m / z): 568 (M ⁺ , ³⁵ Cl); 373; 289; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1465, 1425, 1335, 1130.

[0187]

Example 7-33 Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, Configuration = E Raw material (reference example number) = 4-63. Yield (%) = 83. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.70-3.70 (8H, m), 3.81 (3H, s), 3.846 (6H, s), 3.850 (3
H, s), 3.90 (3H, s), 6.21 (1H, s), 6.54 (2H, s), 6.76-6.8
8 (3H, m), 7.06-7.13 (2H, m), 7.16-7.30 (2H, m). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1515, 1465, 1425, 1330, 1130.

[0188]

Example 7-34 Compound with R ¹ = 3-CH ₃ Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-64. Yield (%) = 83. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.80-3.70 (8H, m), 3.80 (3H, s), 3.85 (3H, s), 3.86 (6H,
s), 3.92 (3H, s), 6.20 (1H, s), 6.55 (2H, s), 6.77-6.90
(3H, m), 7.06-7.28 (4H, m). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1630, 1600, 1590, 151
5, 1465, 1425, 1330, 126
0, 1130.

[0189]

Example 7-35 Compound of R ¹ = 3-ClPh and R ² = 3-ClPh Raw Material (Reference Example Number) = 11. Yield (%) = 86. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.86 (9H, s), 6.36 (1H, s), 6.56 (2H, s), 7.10-7.2
0 (2H, m), 7.27-7.43 (6H, m). Mass spectrum (m / z): 554 (M ⁺ , ³⁵ Cl); 359; 279; 275;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1420, 1330, 1130.

[0190]

Example 7-36 Compound with R ¹ = 4-CH ₃ OPh, R ² = 2-ClPh, Configuration = Z Raw material (reference example number) = 4-66. Yield (%) = 91. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.54 (1H, s), 6.58 (2H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.
29-7.45 (4H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 515; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1685, 1510, 1460, 1420, 1330, 1175, 1130.

[0191]

[Example 7-37] Compound in which R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, and configuration = Z Raw material (reference example number) = 4-69. Yield (%) = 81. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.78 (3H, s), 3.85 (9H, s), 6.35 (1H, s), 6.56 (2H,
s), 6.56-6.94 (3H, m), 7.16-7.40 (5H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1420, 1330, 1125.

[0192]

[Example 7-38] Compound with R ¹ = 3-ClPh, R ² = 3-CH ₃ OPh, configuration = E Raw material (reference example number) = 4-70. Yield (%) = 82. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.77 (3H, s), 3.85 (9H, s), 6.29 (1H, s), 6.54 (2H,
s), 6.80-6.87 (2H, m), 6.90-6.97 (1H, m), 7.12-7.19 (1
H, m), 7.22-7.37 (4H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1585, 1460, 1420, 1330, 1125.

[0193]

[Example 7-39] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh and configuration = Z Raw material (reference example number) = 4-73. Yield (%) = 81. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.85 (9H, s), 6.28 (1H, s), 6.56 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.79Hz), 7.
26-7.40 (4H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1625, 1605, 1585, 151
0, 1460, 1420, 1330, 112
5.

[0194]

Example 7-40 Compound with R ¹ = 3-ClPh, R ² = 4-CH ₃ OPh, Configuration = E Raw material (reference example number) = 4-74. Yield (%) = 82. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (12H, s), 6.21 (2H, s), 6.55 (2H, s), 6.90 (2
H, dm, J = 8.79Hz), 7.20 (2H, dm, J = 8.79Hz), 7.12-7.36 (4
H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1510, 1460, 1420, 1330, 1125.

[0195]

[Example 7-41] Compound in which R ¹ = Ph, R ² = 2-Np, and configuration = Z Raw material (reference example number) = 14. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.50-3.70 (8
H, m), 3.77 (3H, s), 3.82 (6H, s), 6.39 (3H, s), 7.28-7.4
0 (6H, m), 7.46-7.57 (2H, m), 7.78-7.90 (4H, m). Mass spectrum (m / z): 536 (M ⁺ , ³⁵ Cl); 341; 279; 257;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1425, 1330, 1130.

[0196]

[Example 7-42] Compound in which R ¹ = 2-Np, R ² = Ph, and configuration = E Raw material (reference example number) = 15. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.60-3.70 (8
H, m), 3.85 (9H, s), 6.44 (1H, s), 6.54 (2H, s), 7.30-7.5
4 (8H, m), 7.71 (1H, br.s), 7.74-7.88 (3H, m). Mass spectrum (m / z): 536 (M ⁺ , ³⁵ Cl); 341; 279; 257;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1595, 1460, 1420, 1330, 1125.

[0197]

Example 7-43 Compound of R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, Configuration = Z Raw material (reference example number) = 4-77. Yield (%) = 84. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (3H, t, J =
7.32Hz), 1.73-1.90 (2H, m), 3.10-3.70 (8H, m), 3.86 (9
H, m), 3.93 (2H, t, J = 6.35Hz), 6.31 (1H, s), 6.58 (2H, s),
6.86 (2H, dm, J = 8.79Hz), 7.13 (1H, dd, J = 8.30,1.46Hz),
7.17 (2H, dm, J = 8.79Hz), 7.36 (1H, d, J = 1.46Hz), 7.45 (1
H, d, J = 8.30Hz) .Mass spectrum (m / z): 612 (M ⁺ , ³⁵ Cl); 569; 417; 333;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1130.

[0198]

[Example 7-44] Compound in which R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, and configuration = E Raw material (reference example number) = 4-81. Yield (%) = 93. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.47 (3H, t, J =
6.84Hz), 2.50-3.70 (8H, m), 3.80 (3H, s), 3.84 (9H, s),
4.11 (2H, q, J = 6.84Hz), 6.25 (1H, s), 6.53 (2H, s), 6.79 (1
H, br.s), 6.80 (2H, br.s), 7.27-7.34 (2H, m), 7.34-7.41
(3H, m). Mass spectrum (m / z): 560 (M ⁺ , ³⁵ Cl); 545; 365; 281;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0199]

[Example 7-45] Compound in which R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, and configuration = E Raw material (reference example number) = 4-85. Yield (%) = 79. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 0.98 (3H, t, J =
7.32Hz), 1.45-1.58 (2H, m), 1.75-1.90 (2H, m), 2.60-3.
70 (8H, m), 3.79 (3H, s), 3.84 (9H, s), 6.24 (1H, s), 6.53
(2H, s), 6.76-6.86 (3H, m), 7.26-7.34 (2H, m), 7.34-7.4
2 (3H, m). Mass spectrum (m / z): 588 (M ⁺ ); 545; 531; 393; 309;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0200]

Example 7-46 Compound with R ¹ = 4-EtPh, R ² = 3,4-di-ClPh, Configuration = Z Raw material (reference example number) = 4-88. Yield (%) = 81. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.25 (3H, t, J =
7.32Hz), 2.67 (2H, q, J = 7.32Hz), 3.00-3.70 (8H, m), 3.8
6 (9H, m), 6.36 (1H, s), 6.58 (2H, S), 7.13 (1H, dd, J = 8.3
0,1.96Hz), 7.12-7.22 (4H, m), 7.36 (1H, d, J = 1.96Hz),
7.45 (1H, d, J = 8.30Hz) .Mass spectrum (m / z): 582 (M ⁺ , ³⁵ Cl); 387; 303; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1420, 1330, 1130.

[0201]

[Example 7-47] Compound in which R ¹ = 4-PrOPh, R ² = Ph, and configuration = E Raw material (reference example number) = 4-92. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7Hz), 1.50-2.15 (2H, m), 2.80-3.70 (8H, m), 3.83 (9H, s),
3.84 (2H, t, J = 7Hz), 6.26 (1H, s), 6.56 (2H, s), 6.86 (2
H, dm, J = 9Hz), 7.24 (2H, dm, J = 9Hz), 7.25-7.60 (5H, m).

[0202]

Example 7-48 R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, configuration = E
Compound of Example Raw material (reference example number) = 4-93. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 2.60-3.70 (8
H, m), 3.84 (9H, s), 5.98 (2H, s), 6.23 (1H, s), 6.55 (2H,
s), 6.78 (3H, s), 7.20-7.60 (5H, m).

[0203]

[Example 7-49] Compound of R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = 3-CH ₃ Ph, configuration = E Raw material (reference example number) = 4-97. Yield (%) = 69. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (3H, t, J =
7.33Hz), 1.80-1.95 (2H, m), 2.34 (3H, s), 2.70-3.70 (8
H, m), 3.80 (3H, s), 3.85 (9H, s), 3.99 (2H, t, J = 6.84Hz),
6.21 (1H, s), 6.54 (2H, s), 6.80 (3H, br.s), 7.05-7.13
(2H, m), 7.16-7.30 (2H, m). Mass spectrum (m / z): 588 (M ⁺ ); 545; 393; 309; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1630, 1600, 1590, 151
0, 1460, 1425, 1330, 126
0, 1130.

[0204]

Example 7-50 Compound of R ¹ = 3-CH ₃ Ph and R ² = 3-CH ₃ Ph Raw material (Reference example number) = 4-100. Yield (%) = 82. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.34 (6H, s),
2.60-3.70 (8H, m), 3.84 (9H, s), 6.24 (1H, s), 6.54 (2H,
s), 7.02-7.12 (4H, m), 7.13-7.29 (4H, m). Mass spectrum (m / z): 514 (M ⁺ , ³⁵ Cl); 319; 279; 235;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1460, 1425, 1330, 1130.

[0205]

Example 7-51 Compound with R ¹ = 3-PrOPh, R ² = 3-ClPh, Configuration = Z Raw material (reference example number) = 4-103. Yield (%) = 90. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 2.80-3.70 (8H, m), 3.86 (9
H, s), 3.89 (2H, t, J = 6.84Hz), 6.34 (1H, s), 6.56 (2H, s),
6.76-6.85 (2H, m), 6.87-6.94 (1H, m), 7.16-7.40 (5H,
m) .Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 383; 299; 279;
257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1420, 1330, 1125.

[0206]

Example 7-52 Compound with R ¹ = 4-PrOPh, R ² = 3-ClPh, Configuration = Z Raw material (reference example number) = 4-106. Yield (%) = 78. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 3.00-3.70 (8H, m), 3.85 (9
H, m), 3.95 (2H, t, J = 6.35Hz), 6.28 (1H, s), 6.56 (2H, s),
6.85 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.18-
7.22 (1H, m), 7.26-7.40 (3H, m). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 535; 515; 383;
299; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0207]

Example 7-53 Compound with R ¹ = 3-CH ₃ OPh, R ² = 2-ClPh, Configuration = Z Raw material (reference example number) = 4-109. Yield (%) = 77. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.70 (8
H, m), 3.78 (3H, s), 3.86 (9H, s), 6.58 (2H, s), 6.61 (1H,
s), 6.76-6.80 (1H, m), 6.80-6.91 (2H, m), 7.21-7.44 (5
H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 515; 271; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1465, 1425, 1330, 1290, 1130.

[0208]

Example 7-54 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, Configuration = Z Raw material (reference example number) = 4-112. Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.28 (1H, s), 6.57 (2H,
s), 6.87 (2H, dm, J = 8.79Hz), 7.20 (2H, dm, J = 8.79Hz), 7.
. 23-7.30 (2H, m), 7.40-7.46 (1H, m), 7.48-7.57 (1H, m) mass spectrum (m / z): 594 ( M +, 79 Br);
399; 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 16
10, 1590, 1515, 1475, 1430, 1335, 1180, 1130.

[0209]

Example 7-55 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-FPh, Configuration = Z Raw material (reference example number) = 4-116. Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.85 (9H, s), 6.28 (1H, s), 6.56 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 6.94-7.03 (1H, m), 7.04-7.
13 (2H, m), 7.20 (2H, dm, J = 8.79Hz), 7.35 (1H, ddd, J = 7.8
1,7.81,5.86Hz). Mass spectrum (m / z): 535 (M ⁺ ); 339; 279; 255; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1515, 1465, 1430, 1335, 1180, 1130.

[0210]

[Example 7-56] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-CF ₃ Ph, and configuration = Z Raw material (reference example number) = 4-120. Yield (%) = 79. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.846 (6H, s), 3.851 (3H, s), 6.36 (1
H, s), 6.56 (2H, s), 6.87 (2H, dm, J = 8.79Hz), 7.19 (2H, d
m, J = 8.79Hz), 7.45-7.58 (3H, m), 7.62-7.69 (1H, m). Mass spectrum (m / z): 584 (M ⁺ ); 516; 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1425, 1320, 1180, 1130.

[0211]

Example 7-57 Compound with R ¹ = 3-PrOPh, R ² = Ph, Configuration = E Raw material (reference example number) = 4-123. Yield (%) = 89. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.32Hz), 1.70-1.90 (2H, m), 2.70-3.70 (8H, m), 3.84 (6
H, s), 3.85 (3H, s), 3.88 (2H, t, J = 6.35Hz), 6.30 (1H, s),
6.53 (2H, s), 6.78-6.94 (3H, m), 7.19-7.40 (6H, m). Mass spectrum (m / z): 544 (M ⁺ ); 515; 501; 349; 279;
265; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1425, 1330, 1280, 1130.

[0212]

Example 7-58 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-ClPh, Configuration = Z Raw material (reference example number) = 4-127. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.70 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.33 (1H, s), 6.59 (2H,
s), 6.88 (2H, dm, J = 8.78Hz), 7.17 (2H, d, J = 1.95Hz), 7.2
0 (2H, dm, J = 8.78Hz), 7.38 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1560, 1510, 1460, 1420, 1330, 1180, 1130.

[0213]

[Example 7-59] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 2,4-di-ClPh, and configuration = Z Raw material (reference example number) = 4-130. Yield (%) = 93. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.59 (1H, s), 6.61 (2H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.79Hz), 7.
25 (1H, d, J = 8.30Hz), 7.30 (1H, dd, J = 8.30,1,95Hz), 7.44
. (1H, d, J = 1.95Hz) Mass spectrum (m / z): 584 ( M +, 35 Cl); 549; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1515, 1465, 1415, 1335, 1180, 1130.

[0214]

Example 7-60 Compound with R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, Configuration = Z Raw material (reference example number) = 4-132. Yield (%) = 85. Melting point (recrystallization solvent) = 162-164 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.40-3.80 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 6.62 (2H, s), 6.78 (1H,
s), 6.87 (2H, dm, J = 6.83Hz), 7.20-7.30 (3H, m), 7.32-7.
42 (2H, m). Mass spectrum (m / z): 584 (M ⁺ ); 549; 305; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1180, 1130.

[0215]

[Example 7-61] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 2,5-di-ClPh, and configuration = Z Raw material (reference example number) = 4-134. Yield (%) = 85. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.10-3.80 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 6.60 (1H, s), 6.61 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.
26-7.38 (3H, m). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 549; 533; 305;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1630, 1605, 1585, 151
0, 1460, 1420, 1330, 117
5, 1130.

[0216]

[Example 7-62] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 2,3-di-ClPh and configuration = Z Raw material (reference example number) = 4-136. Yield (%) = 89. Melting point (recrystallization solvent) = 119-122 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.20-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.58 (1H, br.s), 6.60
(2H, s), 6.85 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79H
z), 7.23-7.31 (2H, m), 7.46-7.53 (1H, m). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 549; 305; 279;
179. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1280, 1175, 1130.

[0217]

[Example 7-63] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-CH ₃ Ph, and configuration = Z Raw material (reference example number) = 4-139. Yield (%) = 75. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.29 (6H, s),
2.60-3.70 (8H, m), 3.82 (3H, s), 3.846 (6H, s), 3.850 (3
H, s), 6.17 (1H, s), 6.54 (2H, s), 6.85 (2H, dm, J = 8.79H
z), 6.88 (2H, br.s), 7.01 (1H, br.s), 7.21 (2H, dm, J = 8.7
9Hz). Mass spectrum (m / z): 544 (M ⁺ ); 349; 279; 265; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1590, 1505, 1460, 1425, 1330, 1175, 1130.

[0218]

[Example 7-64] Compound in which R ¹ = 4-C ₂ H ₅ -Ph, R ² = 3-Cl-Ph, and configuration = Z Raw material (reference example number) = 4-144. Yield (%) = 78. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.25 (3H, t, J =
7.81Hz), 2.67 (2H, q, J = 7.81Hz), 2.80-3.70 (8H, m), 3.8
5 (9H, s), 6.33 (1H, s), 6.56 (2H, s), 7.14-7.23 (5H, m),
7.25-7.29 (1H, m), 7.31 (1H, dd, J = 7.82,7.82Hz), 7.37 (1
H, ddd, J = 7.82,1.47,1.47Hz). Mass spectrum (m / z): 548 (M ⁺ ); 353; 279; 269; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1465, 1430, 1235, 1130, 985.

[0219]

[Example 7-65] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-CF ₃ Ph, and configuration = Z Raw material (reference example number) = 4-147. Yield (%) = 77. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.20-3.70 (8
H, m), 3.84 (3H, s), 3.86 (9H, s), 6.28 (1H, s), 6.59 (2H,
s), 6.90 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz), 7.
70-7.74 (2H, m), 7.88-7.92 (1H, m). Mass spectrum (m / z): 652 (M ⁺ ); 457; 373; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ). cm-1: 1630, 161
0, 1590, 1515, 1460, 1425, 1330, 1280, 1180, 1130.

[0220]

[Example 7-66] Compound in which R ¹ = 4-EtOPh, R ² = 3,5-di-ClPh, and configuration = Z Raw material (reference example number) = 4-151. Yield (%) = 82. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.43 (3H, t, J =
6.84Hz), 3.20-3.70 (8H, m), 3.86 (9H, s), 4.05 (2H, q, J =
6.84Hz), 6.33 (1H, s), 6.59 (2H, s), 6.86 (2H, dm, J = 8.79
Hz), 7.166 (2H, d, J = 1.95Hz), 7.167 (2H, dm, J = 8.79Hz),
7.38 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 598 (M ⁺ ); 403; 319; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1220, 1175, 1130.

[0221]

[Example 7-67] Compound in which R ¹ = 4-EtPh, R ² = 3,5-di-ClPh, and configuration = Z Raw material (reference example number) = 4-155. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.25 (3H, t, J =
7.32Hz), 2.67 (2H, q, J = 7.32Hz), 3.00-3.75 (8H, m), 3.8
6 (9H, s), 6.38 (1H, s), 6.59 (2H, s), 7.1O-7.26 (4H, m),
7.17 (2H, d, J = 1.95Hz), 7.38 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 582 (M ⁺ ); 387; 303; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1560, 1460, 1425, 1330, 1220, 1130.

[0222]

[Example 7-68] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-FPh, and configuration = Z Raw material (reference example number) = 4-159. Yield (%) = 95. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.05-3.75 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.33 (1H, s), 6.59 (2H,
s), 6.77-6.91 (3H, m), 6.87 (2H, dm, J = 8.79Hz), 7.19 (2
H, dm, J = 8.79Hz). Mass spectrum (m / z): 552 (M ⁺ ); 357; 279; 273; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1625, 1610, 1595, 151
5, 1465, 1430, 1335, 118
0, 1130.

[0223]

[Example 7-69] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-CNPh, and configuration = Z Raw material (reference example number) = 4-162. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.80 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.41 (1H, s), 6.59 (2H,
s), 6.88 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.79Hz), 7.
45-7.60 (3H, m), 7.62-7.72 (1H, m). Mass spectrum (m / z): 541 (M ⁺ ); 346; 279; 262; 195. Infrared absorption spectrum ν _max (CHCl ₃ ). cm-1: 2220, 162
5, 1605, 1585, 1510, 1460, 1420, 1330, 1175, 1125.

[0224]

Example 7-70 Compound with R ¹ = 4-EtOPh, R ² = 3-FPh, Configuration = Z Raw material (reference example number) = 4-165. Yield (%) = 94. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.42 (3H, t, J =
6.83Hz), 2.70-3.70 (8H, m), 3.85 (9H, s), 4.05 (2H, q, J =
6.83Hz), 6.28 (1H, s), 6.56 (2H, s), 6.85 (2H, dm, J = 8.79
Hz), 6.93-7.03 (1H, m), 7.03-7.13 (2H, m), 7.19 (2H, dm,
J = 8.79Hz), 7.35 (1H, ddd, J = 7.81,7.81,5.86Hz) .Mass spectrum (m / z): 548 (M ⁺ ); 533; 519; 353; 279;
269; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1585, 1505, 1460, 1420, 1330, 1170, 1125.

[0225]

Example 7-71 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-Cl-5-Me-Ph, Configuration = Z Raw material (reference example number) = 4-169. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
2.70-3.70 (8H, m), 3.83 (3H, s), 3.86 (9H, s), 6.25 (1H,
s), 6.57 (2H, s), 6.86 (2H, dm, J = 8.79Hz), 6.93-7.11 (2
H, m), 7.14-7.25 (1H, m), 7.20 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 564 (M ⁺ , ³⁵ Cl); 549; 369; 285;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1510, 1460, 1420, 1330, 1170, 1125.

[0226]

[Example 7-72] Compound in which R ¹ = 4-EtOPh, R ² = 3-Cl-5-Me-Ph, and configuration = Z Raw material (reference example number) = 4-173. Yield (%) = 92. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.40 (3H, t, J =
7Hz), 2.32 (3H, s), 2.90-3.75 (8H, m), 3.85 (9H, s), 4.0
4 (2H, q, J = 7Hz), 6.26 (1H, s), 6.59 (2H, s), 6.80-7.40 (3
H, m), 6.86 (2H, dm, J = 9Hz), 7.22 (2H, q, J = 9Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 563; 383; 299;
279; 195.

[0227]

Example 8 1- [E-3,5-diphenylpent-2-ene-4-inoyl] -4
-(3,4,5-Trimethoxybenzoyl) -piperazine Using the compound of Reference Example 6 (0.900 g) and in the same manner as in Example 1, the title compound (1.574 g) was obtained as a powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.40-4.00 (8
H, m); 3.83 (3H, s); 3.85 (6H, s); 6.59 (2H, s); 6.74 (1H,
s); 7.3-7.8 (10H, m). Mass spectrum (m / z): 510 (M ⁺ ); 315; 279; 231; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
⁻¹ : 1615, 1590, 1490, 146
0, 1420, 1330, 1125. Elemental analysis _{(C 31 H 30 N 2 O} 5 ) Calculated value: C; 72.97, H; 5.92 , N; 5.49 Found:. C; 72.65, H; 6.10, N; 5.45.

[0228]

Example 9 1-[(2E, 4Z) -3,5-diphenylpent-2,4-dienoyl]-
4- (3,4,5-Trimethoxybenzoyl) piperazine To a solution of the compound of Example 8 (0.250 g) in methanol (5 ml) was added 10% palladium-barium sulfate (0.025 g) and quinoline (2 drops). Hydrogen gas was passed through at room temperature and atmospheric pressure. After reacting for 15 hours, the catalyst was filtered off and the solvent was distilled off. The residue was subjected to medium pressure liquid chromatography using a Roper B column, and methylene chloride-ethyl acetate (3: 2 to 1: 3)
The title compound (0.153 g) was obtained as a powder from the fraction eluted with. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.80 (8
H, m), 3.86 (3H, s), 3.87 (6H, s), 6.38 (1H, br.s), 6.58
(2H, s) 6.61 (1H, dd, J = 12.20,1.95Hz).

[0229]

Example 10 1- [3,3-bis (4-methoxyphenyl) -2-methylacrylo
Iyl ] -4- (3,4,5-trimethoxybenzoyl) piperazine Using the compound of Reference Example 9 (0.511 g) and in the same manner as in Example 7, the title compound (0.673 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.00 (3H, s);
2.95-3.45 (8H, m); 3.80 (3H, s); 3.82 (3H, s); 3.846 (6H,
s); 3.851 (3H, s); 6.53 (2H, s); 6.75-7.20 (8H, m). Mass spectrum (m / z): 560 (M ⁺ ); 545; 365; 281; 279;
195.

[0230]

Example 11 1- (3,3-diphenylacryloyl) -4- (3,4,5-trimetho)
Xybenzenesulfonyl) piperazine 3-phenyl cinnamic acid (0.400 g) in methylene chloride (8 ml)
Phosphorus pentachloride (0.371 g) was added to the solution under ice cooling. 0-5
After stirring at ℃ for 1 hour, the reaction solution was concentrated. Dry toluene (10 ml) was added to the residue, and the mixture was concentrated and dried. The residue was dissolved in tetrahydrofuran (5 ml) and the compound of Reference Example 10 (0.
564 g), sodium hydrogen carbonate (0.300 g), tetrahydrofuran (15 ml) and water (7.5 ml). After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted twice with methylene chloride. Wash the extract with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and brine, and dry.
Concentrated. The residue was subjected to column chromatography using silica gel (20 g). The title compound (0.750 g) was obtained as crystals from the fraction eluted with methylene chloride-ethyl acetate. Melting point: 163-165 ° C. (ethyl acetate-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.17 (2H, t, J =
4.76Hz); 2.81 (2H, t, J = 4.76Hz); 3.35 (2H, t, J = 4.76Hz);
3.64 (2H, t, J = 4.76Hz); 3.92 (6H, s); 3.97 (3H, s); 6.21
(1H, s); 6.80 (2H, s); 7.00-7.40 (10H, m). Mass spectrum (m / z): 522 (M ⁺ ); 458; 315; 291; 231;
207. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 159
5, 1500, 1460, 1410, 1350, 1315, 1155, 1130. Elemental analysis (as C ₂₈ H ₃₀ N ₂ O ₆ S) Calculated: C; 64.35, H; 5.79, N; 5.36, S; 6.14. Found: C; 64.60, H; 5.94, N; 5.35, S; 6.27.

[0231]

Example 12 1- (3-phenylcinnamoyl) -4- (3,4,5-trimethoxy
Thiobenzoyl) piperazine 3-phenylcinnamic acid (0.900 g) in methylene chloride (18 ml)
Phosphorus pentachloride (0.836 g) was added to the solution under ice cooling, and the mixture was cooled to 0-5 ° C.
It was stirred for 1 hour. After concentrating and drying the reaction solution, dry toluene (20 ml) was added and concentration and drying were repeated. The residue was dissolved in tetrahydrofuran (5 ml), 1- (3,4,5-trimethoxythiobenzoyl) piperazine (1.189 g), sodium hydrogen carbonate (0.674 g), tetrahydrofuran (25 m
It was added under water cooling into a mixture of l) and water (12.5 ml).
After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted twice with methylene chloride. The extract was washed successively with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water, dried and concentrated. The residue was subjected to column chromatography using silica gel (40 g), methylene chloride-ethyl acetate.
Fractions eluted at (3: 1) were collected and the title compound (1.860
g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.84 (1H, br.
s); 3.23 (1H, br.s); 3.39 (1H, br.s); 3.51 (2H, br.s);
3.69 (1H, br.s); 3.76 (1H, br.s); 3.82,3.84 (9H, s × 2);
4.17 (1H, br.s); 6.27,6.33 (1H, s x 2); 6.37,6.44 (2H, s
× 2); 7.20-7.50 (10H, m). Mass spectrum (m / z): 502 (M ⁺ ); 469; 335; 295; 211;
207; 178; 167. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 158
0, 1460, 1425, 1340, 1280, 1125.

[0232]

Example 13 1- [3,3-bis (4-methoxyphenyl) acryloyl] -4-
(3,4,5-Trimethoxythiobenzoyl) piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (0.400
g) in the same manner as in Example 12 to give the title compound (0.59
6 g) was obtained as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.96, 3.23, ₃ .
45,3.51,4.20 (8H, br.s × 5); 3.82 (6H, s); 3.85 (9H, s);
6.11,6.16 (1H, s × 2); 6.38,6.45 (2H, s × 2); 6.80-6.95
(4H, m); 7.10-7.30 (4H, m). Mass spectrum (m / z): 562 (M ⁺ ); 529; 335; 295; 267;
227; 211. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
⁻¹ : 1625, 1605, 1585, 151
0, 1460, 1425, 1340, 128
0, 1170, 1125. Elemental analysis value (as C ₃₁ H ₃₄ N ₂ O ₆ S) Calculated value: C; 66.17, H; 6.09, N; 4.98, S; 5.70. Found value: C; 65.92, H; 6.37, N; 4.84, S 5.65.

[0233]

Example 14 1- [3,3-bis (4-fluorophenyl) -4- (3,4,5-trimethyl)
Toxithiobenzoyl) piperazine 3,3-bis (4-fluorophenyl) acrylic acid (0.300 g)
And the title compound (0.574
g) was obtained as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.04, 3.25, ₃ .
52,3.78,4.21 (8H, br.s × 5); 3.84 (9H, s); 6.28 (1H, br.
s); 6.45 (2H, s); 6.95-7.35 (8H, m). Mass spectrum (m / z): 538 (M ⁺ ); 505; 335; 295; 243;
211. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
0, 1580, 1505, 1460, 1425, 1340, 1125.

[0234]

Example 15 1- (3-Phenylcinnamoyl) -4- (3,4,5-trimethoxy
Benzyl) piperazine 3-phenylcinnamic acid (0.500 g) and 1- (3,4,5-trimethoxybenzyl) piperazine (0.653 g) were operated as in Example 12 to give the title compound (0.897). g) was obtained as a powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.88 (2H, t, J =
5.13Hz); 2.25 (2H, t, J = 5.13Hz); 3.28 (2H, m); 3.28 (2H,
s); 3.55 (2H, t, J = 5.13Hz), 3.83 (3H, s); 3.84 (6H, s);
6.30 (1H, s); 6.46 (2H, s); 7.13-7,47 (10H, m). Mass spectrum (m / z): 472 (M ⁺ ); 457; 291; 265; 207;
181. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 159
5, 1460, 1440, 1345, 1125.

[0235]

Example 16 1- (3,3-diphenylthioacryloyl) -4- (3,4,5-tri
(Methoxythiobenzoyl) piperazine Compound of Example 12 (1.000 g) and Lawesson
A solution of the reagent (0.805 g) in benzene (10 ml) was heated under reflux for 2 hours. After allowing to cool, pour the reaction mixture into water and wash with ethyl acetate.
Extracted twice. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (30 g). Fractions eluted with hexane-ethyl acetate (3: 1) were collected to give the title compound (1.010 g) as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.86-4.45 (8
H, m); 3.82,3.84 (9H, s × 2); 6.36,6.37 (2H, s × 2); 6.6
6,6.69 (1H, s × 2); 7.15-7.50 (10H, m). Mass spectrum (m / z): 518 (M ⁺ ); 485; 351; 307. Infrared absorption spectrum ν _max (CHCl ₃ ). cm ^-1 : 1580, 147
5, 1425, 1340, 1285, 1130.

[0236]

Example 17 1- [3,3-bis (4-methoxyphenyl) thioacryloyl
-4- (3,4,5-Trimethoxybenzoyl] piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (3.00 g) and triethylamine (2.94 ml) in methylene chloride (6
Diphenylphosphoric acid azide (3.41 ml) and 1-formylpiperazine (1.09 ml) were added to 0 ml), and the mixture was stirred at room temperature for 2 hours.
The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was dissolved in methanol (80 ml). After adding 10% aqueous sodium hydroxide solution (40 ml) and stirring at room temperature for 18 hours, the reaction solution was poured into water and extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (80 g). Fractions eluted with methylene chloride-methanol (19: 1-4: 1) were collected and combined with 1- [3,3-bis (4-methoxyphenyl)
Acryloyl] piperazine (3.00 g) was obtained as a powder. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 2.0
8 (1H, s); 2.20-3.65 (8H, m);
3.80 (6H, s); 6.13 (1H, s);
6.70-7.40 (8H, m). The above compound (1.155 g) and Lawesson's reagent (1.3
A solution of 26 g) in benzene (12 ml) was heated under reflux for 2 hours. After allowing to cool, the reaction solution was poured into water and extracted twice with ethyl acetate. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (30 g).
Fractions eluted with methylene chloride-methanol (19: 1) were collected to give 1- [3,3-bis (4-methoxyphenylthioacryloyl] piperazine (1.177 g) as a powder NMR spectrum (60 MHz , CDCl ₃ ) δ ppm: 2.30 (2H, m);
2.80 (2H, m); 2.86 (1H, s); 3.48 (2H, m); 3.80 (6H, s); 4.
16 (2H, m); 6.50 (1H, s); 6.70-7.50 (8H, m). The above thioamide (1.049 g) and triethylamine
(0.29 ml) in methylene chloride (30 ml) under ice cooling.
3,4,5-Trimethoxybenzoyl chloride (0.157g) was added. After stirring at room temperature for 1 hour, the reaction solution was poured into water,
It was extracted twice with methylene chloride. The extract was washed successively with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water, dried and concentrated. The residue was subjected to column chromatography using silica gel (40 g) and medium pressure liquid chromatography using a Rover B column. Methylene chloride
Fractions eluting with ethyl acetate (9: 1-4: 1) were collected to give the title compound (1.368 g) as a yellow powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.75-3.30 (2
H, m); 3.40-3.70 (4H, m); 3.83,3.846,3.850 (15H, s × 3);
6.53,6.55 (3H, s × 2); 6.80-6.95 (4H, m); 7.15-7.35 (4H,
m). Mass spectrum (m / z): 562 (M ⁺ ); 529; 455; 367. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1280, 1170, 1125.

[0237]

Example 18 1- [3,3-bis (4-methoxyphenyl) thioacryloyl
]]-4- (3,4,5-Trimethoxythiobenzoyl) piperazide
The title compound (0.792 g) was obtained as a yellow powder in the same manner as in Example 16 using the compound of Example 17 (0.790 g). NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.99,3.46,
3.56,3.72,4.27,4.37 (8H, br.s × 6); 3.82,3.83,3.85 (15
H, s × 3); 6.39,6.46 (2H, s × 2); 6.51,6.55 (1H, s × 2);
. 6.80-6.95 (4H, m); 7.10-7.37 (4H, m) Mass spectrum (m / z): 578 ( M +); 545; 513; 367. Infrared absorption spectrum ν _max (CHCl ₃₎ cm ^{- 1} : 1605, 158
0, 1510, 1460, 1425, 1335, 1280, 1170, 1125. Elemental analysis value (as C ₃₁ H ₃₄ N ₂₀ O ₅ S ₂ ) Calculated value: C; 69.34, H; 5.92, N; 4.84, S; 11.08 Actual value: C; 64.21, H; 6.19, N; 4.64, S; 10.98.

[0238]

Example 19 1- [3,3-Bis (3-chlorophenyl) acryloyl] -4-
(3,4-Dimethoxybenzoyl) piperazine 3,4-dimethoxybenzoic acid (0.250 g) and triethylamine (0.38 ml) in methylene chloride (10 ml) were dissolved in diphenylphosphoryl azide (0.44 ml) and the compound of Reference Example 12 (0.545). g) was added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed successively with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water, dried and concentrated. The residue was applied to Lobar-B column (2
Fractions eluted with hexane-ethyl acetate (1: 2-1: 4) were collected to give the title compound (0.682 g) as a white powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.70 (8
H, m); 3.890 (3H, s); 3.90 (3H, s); 6.36 (1H, s); 6.85 (1
H, d, J = 7.81Hz); 6.92 (1H, dd, J = 7.81,1.47Hz); 6.95 (1H,
d, J = 1.47Hz); 7.10-7.20 (2H, m); 7.24-7.42 (6H, m). Mass spectrum (m / e): 524 (M ⁺ , ³⁵ Cl); 359; 275; 249;
165.

[0239]

Example 20 1- [3,3-bis (3-chlorophenyl) acryloyl] -4- (4
-Methoxybenzoyl) piperazine Compound of Reference Example 12 (0.529 g) and triethylamine (0.4
1 ml) in methylene chloride (10 ml) under ice cooling, p
-Methoxybenzoic acid chloride (0.250 g) was added, and the mixture was stirred at room temperature for 1 hour.
Stir for hours. Thereafter, the same operation as in Example 19 is carried out,
The title compound (0.682 g) was obtained as a powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.70 (8
H, m); 3.83 (3H, s); 6.36 (1H, s); 6.90 (1H, dm, J = 8.79H
z); 7.10-7.19 (2H, m); 7.24-7.42 (8H, m). Mass spectrum (m / e): 494 (M ⁺ , ³⁵ Cl); 359; 275; 219;
135. Elemental analysis _{(C 27 H 24 Cl 2 N} 2 as O ₃₎ Calculated: C; 65.46, H; 4.88 , N; 5.65, Cl; 14.31 Found:. C; 65.19, H; 5.12, N; 5.64, Cl; 14.55.

[0240]

Example 21 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (4-acetoxy-3,5-dimethoxyben
Zoyl) piperazine Compound of Reference Example 23 (0.600 g) and compound of Reference Example 22
The target compound (1.072 g) was obtained as a powder in the same manner as in Example 19 using (0.936 g). Melting point: 191-194 ° C NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H,
s); 2.70-3.70 (8H, m); 3.82 (6H, s); 3.83 (3H, s); 6.28
(1H, s); 6.58 (2H, s); 6.87 (2H, dm, J = 8.79Hz); 7.16-7.2
3 (3H, m); 7.32 (1H, dd, J = 7.32,7.32Hz); 7.37 (1H, ddd, J =
7.81,1.95,1.95Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 536; 355; 307;
271; 18 1. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1770, 163
0, 1600, 1515, 1460, 1430, 1370, 1340, 1285, 1180,
1135.

[0241]

Example 22 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (3,5-dimethoxy-4-hydroxyben
Zoyl) piperazine To a solution of the compound of Example 21 (0.500 g) in methanol (20 ml) was added saturated aqueous potassium carbonate solution (10 ml), and the mixture was stirred at room temperature for 1 hr. The reaction solution was poured into water and extracted with methylene chloride three times. The extract is washed with water, dried and concentrated,
The residue was subjected to medium pressure liquid chromatography using a Rover-B column (2). Ethyl acetate-methanol (19:
Fractions eluted in 1) were collected to obtain the target compound (0.464g) as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.00-3.70
(8H, m); 3.83 (3H, s); 3.89 (6H, s); 5.72 (1H, s); 6.29 (1
H, s); 6.61 (2H, s); 6.87 (2H, dm, J = 9.27Hz); 7.16-7.23
(3H, m); 7.31 (1H, dd, J = 8.30,8.30Hz); 7.37 (1H, ddd, J =
8.30,1.95,1.95Hz). Mass spectrum (m / z): 536 (M ⁺ ); 356; 355; 271; 265;
181. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3550, 163
0, 1605, 1510, 1460, 1420, 1365, 1330, 1280, 1180,
1115, 980, 830.

[0242]

Example 23 1- [Z-3- (4-methoxyphenyl) -3- (3-trifluoromethyi)
Luphenyl) acryloyl] -4- (3,4,5-trimethoxybutene
Nazoyl) hexahydro-1H-1,4-diazepine Condensation reaction of the compound of Reference Example 4-120 (0.516 g) with 1- (3,4,5-trimethoxybenzoyl) homopiperazine (0.471 mg) and its reaction product. Was produced in the same manner as in Example 7 to obtain the target compound (0.819 g) as a powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.60-2.10
(2H, m); 3.20-3.80 (8H, m); 3.82 (3H, s); 3.83 (3H, s);
3.85 (3H, s); 3.86 (3H, s); 6.46 (1H, br.s); 6.55 (2H, s);
6.81-6.92 (2H, m); 7.14-7.25 (2H, m); 7.40-7.52 (2H, m
m); 7.52-7.66 (2H, m). Mass spectrum (m / z): 598 (M ⁺ ); 403; 305; 293; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1590, 1510, 1465, 1420, 1320, 1180, 1130.

[0243]

Example 24 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (2-pyridinecarbonyl) piperazine The compound of Reference Example 22 (0.500 g) and triethylamine (0.4
4 mg) in tetrahydrofuran (10 ml), pyridine-
2-Carboxylic acid chloride hydrochloride (0.249 g) was added under ice cooling. After stirring at room temperature for 3 days, the solvent was distilled off. The residue was dissolved in methylene chloride, washed with water, dried and concentrated. The residue was subjected to medium pressure liquid chromatography using a Rover B column (2), and methylene chloride-
Collect the fractions eluted with methanol (49: 1) to obtain the desired compound.
(0.489 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.10-3.75
(8H, m); 3.83 (3H, s); 6.28,6.31 (1H, s × 2); 6.80-6.92
(2H, m); 7.15-7.40 (7H, m); 7.68 (1H, br.d, J = 7.81Hz);
7.80 (1H, br.dd, J = 7.81,7.81Hz); 8.50-8.62 (1H, m). Mass spectrum (m / z): 461 (M ⁺ , ³⁵ Cl); 433; 355; 271;
190; 106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1570, 1515, 1480, 1460, 1440, 1425, 1290, 1250,
1175, 1010, 830. Elemental analysis (C ₂₆ H ₂₄ ClN ₃ as O ₃₎ Calculated: C; 67.60, H; 5.24 , N; 9.10 Found:. C; 67.64, H; 5.58, N; 9.10.

[0244]

Example 25 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (3-pyridinecarbonyl) piperazine Using the compound of Reference Example 22 (0.500 g) and pyridine-3-carboxylic acid chloride hydrochloride (0.249 g), and performing the same procedure as in Example 24 to obtain the target compound ( 0.548 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.80-3.80
(8H, m); 3.83 (3H, s); 6.28 (1H, s); 6.87 (2H, dm, J = 8.78H
z); 7.15-7.42 (7H, m); 7.71 (1H, dm, J = 7.81Hz); 8.61 (1
H, br.s); 8.65-8.72 (1H, m). Mass spectrum (m / z): 461 (M ⁺ , ³⁵ Cl); 433; 355; 271;
190; 106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
⁻¹ : 1630, 1605, 1510, 146
0, 1430, 1420, 1290, 125
0, 1180, 1140, 1005, 830. Elemental analysis _{(C 26} H 24 _ClN 3 as _{O 3)} Calculated: C; 67.60, H; 5.24 , N; 9.10, Cl; 7.67 Found:. C; 67.49, H; 5.54, N; 9.09, Cl; 7.44.

[0245]

Example 26 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (4-pyridinecarbonyl) piperazine A compound of Reference Example 22 (0.500 g) and pyridine-4-carboxylic acid chloride hydrochloride (0.299 g) were prepared in the same manner as in Example 24 to obtain the target compound ( 0.612 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.80
(8H, m); 3.83 (3H, s); 6.28 (1H, br.s); 6.87 (2H, dm, J = 8.
30Hz); 7.10-7.42 (8H, m); 8.70 (2H, dm, J = 4.88Hz) .Mass spectrum (m / z): 461 (M ⁺ , ³⁵ Cl); 355; 271; 190;
106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1510, 1460, 1430, 1285, 1240, 1175, 1010, 830. Elemental analysis (C ₂₆ H ₂₄ ClN ₃ as O ₃₎ Calculated: C; 67.60, H; 5.24 , N; 9.10, Cl; 7.67 Actual value: C; 67.43, H; 5.48, N; 9.11, Cl; 7.50.

[0246]

Example 27 1- [Z-3- (3,5-dichlorophenyl) -3- (4-methoxyphenyl)
A) Acryloyl] -4- (3-pyridinecarbonyl) pipera
Gin Using the compound of Reference Example 28 (0.500 g) and pyridine-3-carboxylic acid chloride hydrochloride (0.250 g), and in the same manner as in Example 24, the title compound (0.587 g) was obtained as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 2.95-3.80
(8H, m); 3.84 (3H, s); 6.34 (1H, s); 6.88 (2H, dm, J = 8.79H
_Z ); 7.16 (2H, d, J = 1.96H _Z ); 7.18 (2H, dm, J = 8.79H _Z ); 7.3
2-7.43 (1H, m); 7.39 (1H, t, J = 1.96H _Z ); 7.74 (1H, ddd, J =
7.81,1.46,1.46H _Z ); 8.60-8.70 (1H, m); 8.69 (1H, dd, J =
4.88,1.46H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1510, 1460, 1430, 1415, 1285, 1250, 1175, 1005. Mass spectrum (m / z): 495 (M ⁺ , ³⁵ Cl); 389; 305; 190;
106.

[0247]

Example 28 dl-7-bis (4-methoxyphenyl) methylene-2- (3,4,5
-Trimethoxy) benzoyl octahydropyrrolo [1,2-
a] Pyrazin -6-one Under a nitrogen atmosphere, a solution of diisopropylamine (0.424 ml) in tetrahydrofuran (24 ml) was added dropwise with a hexane solution of n-butyllithium (1.6M, 1.89 ml) at -78 ° C. After stirring for 30 minutes under ice-cooling, the mixture was cooled to -78 ° C, and the compound of Reference Example 44 (843.6 mg) and hexamethylphosphoric triamide (12 m
A mixed solution of l) and tetrahydrofuran (16 ml) was added dropwise. After stirring at -78 ° C for 5 minutes, 4,4'-dimethoxybenzophenone (672.4 mg) and hexamethylphosphoric triamide were added.
A solution of (4 ml) and tetrahydrofuran (16 ml) was added dropwise. After stirring at -78 ° C for 1 hour, a solution of acetic acid (0.175 ml) in tetrahydrofuran (0.4 ml) was added dropwise. The reaction solution was poured into ethyl acetate and water and washed 3 times with water. The organic layer was washed with saturated brine, dried and concentrated. Silica gel (16
g), column chromatography was performed, and the fractions eluted with methylene chloride methanol (99.5: 0.5-99: 1) were collected to give dl-7- {bis (4-methoxyphenyl)} hydroxymethyl-2. -(3,4,5-Trimethoxy) benzoyloctahydropyrrolo [1,2-a] pyrazin-6-one (730.3 mg, yield 50%) was obtained as an oil. The above compound (728.0 mg) and p-toluenesulfonic acid monohydrate (48.0 mg) were heated under reflux in toluene (15 ml) for 3 hours. After cooling, the reaction solution was poured into water and extracted 3 times with ethyl acetate. The extracts were combined and washed with a saturated aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution. The residue obtained by drying and concentrating is purified by silica gel (14
column chromatography with g) and hexane
-The fractions eluted with ethyl acetate (1: 4-0: 1) were collected to give the title compound (662.9 mg, yield 94%) as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 2.50-3.10
(7H, m); 3.50-3.70 (1H, m); 3.81 (6H, s); 3.86 (9H, s);
4.10-4.25 (1H, m); 6.62 (2H, s); 6.84 (4H, dm, J = 8.79H _Z );
7.10 (4H, dm, J = 8.79H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1685, 163
0, 1605, 1575, 1510, 1460, 1420, 1330, 1125. Mass spectrum (m / z): 558 (M ⁺ ); 363; 195.

[0248]

Example 29 dl-7-bis (4-chlorophenyl) methylene-2- (3,4,5-to)
Limethoxy) benzoyl octahydro-2H-pyrido [1,2-
a] Under a nitrogen atmosphere of pyrazin-6-one, a hexane solution of n-butyllithium (1.6M, 0.87 ml) was added dropwise to a solution of diisopropylamine (0.194 ml) in tetrahydrofuran (9 ml) at -78 ° C. After stirring under ice cooling for 30 minutes, the mixture was cooled to -78 ° C, and the compound of Reference Example 51 (402.2 mg) and hexamethylphosphoric triamide (5 ml) were added.
And a mixed solution of tetrahydrofuran (3 ml) was added dropwise.
After stirring the reaction solution for 30 minutes under ice cooling, it was cooled to -78 ° C,
4,4'-Dichlorobenzophenone (318.8 mg) and hexamethylphosphoric triamide (1 ml) and tetrahydrofuran (6 ml)
The mixed solution of was added dropwise. After stirring at -78 ° C for 1 hour, acetic acid was added.
A solution of (0.080 ml) in tetrahydrofuran (0.2 ml) was added dropwise. Thereafter, the same operation as in Example 28 is carried out to give the indicated compound.
(432.5 mg) was obtained as white crystals. . Yield: 54% (2 steps) mp: 181.0-183.0 ° C. (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.50-1.70
(1H, m); 2.00-2.20 (1H, m); 2.40-2.90 (6H, m); 2.95-3.2
0 (1H, m); 3.45-3.60 (1H, m); 3.87 (9H, s); 4.55-4.75 (1
H, m); 6.63 (2H, s); 7.00 (2H, dm, J = 2.93H _Z ); 7.03 (2H, d
m, J = 2.93H _Z ); 7.25 (2H, dm, J = 8.79H _Z ); 7.30 (2H, dm, J = 8.7
9H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1625, 158
5, 1490, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 195. Elemental analysis value: Calculated as C ₃₁ H ₃₀ Cl ₂ N ₂ O ₅ : C; 64.03, H; 5.20, Cl; 12.19, N; 4.82. Measurements: C; 64.05, H; 5.38, Cl; 12.35, N; 4.87.

[0249]

Example 30 dl-7-bis (4-methoxyphenyl) methylene-2- (3,4,5
-Trimethoxy) benzoyl octahydro-2H-pyrido
[1,2-a] Pyrazin -6-one Starting from the compound of Reference Example 51 (524.5 mg) and 4,4′-dimethoxybenzophenone (401 mg), in the same manner as in Example 29, the title compound (486.4 mg) was obtained as white crystals. . Yield: 58% (2 steps) mp: 163.0-164.0 ° C. (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.50-1.70
(1H, m); 2.00-2.15 (1H, m); 2.40-2.90 (6H, m); 2.95-3.2
0 (1H, m); 3.45-3.60 (1H, m); 3.78 (3H, s); 3.81 (3H, s);
3.87 (9H, s); 4.60-4.80 (1H, m); 6.63 (2H, s); 6.80 (2H, d
m, J = 8.79H _Z ); 6.84 (2H, dm, J = 8.79H _Z ); 7.00 (2H, dm, J = 1.4
6H _Z ); 7.03 (2H, dm, J = 1.46H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1585, 1505, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 572 (M ⁺ ); 377; 195.

[0250]

Example 31 (S) -7-{(Z)-(3,5-dichlorophenyl)-(4-methoxyphen
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoyl
Kutahydropyrrolo [1,2-a] pyrazin-6-one Using the compound of Reference Example 45 (2.010 g) and 3,5-dichloro-4′-methoxybenzophenone (1.859 g), the same operation as in Example 28. did. The crude product was loaded onto a roller column (C
Column) and the low-polarity fractions eluted with methylene chloride-methanolsan (99: 1) were collected to obtain 0.314 g of the target compound (8.1% in 2 steps) as a powder. [Α] _D ²⁵ + 51.8 ° (c = 1.01, CHCl ₃ ) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.50-3.15 (7
H, m), 3.55-3.75 (1H, m), 3.82 (3H, s), 3.86 (9H, s), 4.05
-4.25 (1H, m), 6.63 (2H, s), 6.87 (2H, br.dm, J = 8.79Hz),
7.05 (2H, d, J = 1.95Hz), 7.10 (2H, br.dm, J = 8.79Hz), 7.29
. (1H, t, J = 1.95Hz) Mass spectrum (m / z): 596 ( M +, 35 Cl); 401; 195. Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1: 1680, 163
0, 1610, 1590, 1560, 1510, 1465, 1415, 1330, 1250,
1130.

[0251]

Example 32 (S) -7-{(E)-(3,5-dichlorophenyl)-(4-methoxyphen)
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoyl
Kutahydropyrrolo [1,2-a] pyrazin-6-one After eluting the compound of Example 31, elution was further continued, and highly polar fractions were collected to obtain 1.968 g of the target compound (55. 4%) was obtained as a powder. [Α] _D ²⁵ + 38.2 ° (c = 1.03, CHCl ₃ ) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.35-3.15 (7
H, m), 3.50-3.75 (1H, m), 3.81 (3H, s), 3.86 (3H, s), 3.87
(6H, s), 4.05-4.30 (1H, m), 6.63 (2H, s), 6.86 (2H, dm, J =
8.79Hz), 7.05 (2H, br.d, J = 1.95Hz), 7.10 (2H, dm, J = 8.79
Hz), 7.28-7.31 (1H, m). Mass spectrum (m / z): 596 (M ⁺ , ³⁵ Cl); 401; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1680, 163
0, 1610, 1585, 1560, 1510, 1465, 1415, 1330, 1245,
1130.

[0252]

Example 33 (R) -7-{(Z)-(3,5-dichlorophenyl)-(4-methoxyphen
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoyl
Kutahydropyrrolo [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 46 and in the same manner as in Example 31, the target compound was obtained as a powder. [Α] _D ²⁵ -51.3 ° (c = 1.05, CHCl ₃ )

[0253]

Example 34 (R) -7-{(E)-(3,5-dichlorophenyl)-(4-methoxyphen
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoyl
Kutahydropyrrolo [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 46 and following the procedure of Example 32, the target compound was obtained as a powder. [Α] _D ²⁵ -37.9 ° (c = 1.08, CHCl ₃ )

[0254]

Reference Example 1 Diethylphosphonoacetic acid was added to a suspension of (E)-and (Z) -3- (2-thienyl) sodium cinnamate hydride (5.63 g, content 55%) in tetrahydrofuran (400 ml). ethyl
(26.30 g) in tetrahydrofuran (100 ml) under ice cooling
It was added dropwise at 8-10 ° C over 15 minutes. The reaction mixture was stirred at room temperature for 1 hr, 2-benzoylthiophene (22.08 g) was added, and the mixture was further heated under reflux for 21 hr. The reaction solution was poured into water (300 ml) and extracted with ethyl acetate. After the extract was dried over sodium sulfate, the solvent was distilled off. Oily residue (26.56
g) was dissolved in methanol (450 ml), 10% aqueous sodium hydroxide solution (150 ml) was added, and the mixture was stirred at room temperature for 2 hr. The reaction solution was poured into water (500 ml) and washed with methylene chloride. The aqueous layer was adjusted to pH 2 with hydrochloric acid and extracted with methylene chloride. The extract was dried over sodium sulfate, the solvent was evaporated, and the residue was subjected to column chromatography using silica gel. Methylene chloride-methanol (19:
Isomer A showing lower polarity when eluted in 1)
(Presumed to be the (Z) -isomer) [Rf value: 0.48 (silica gel, methylene chloride-methanol (24: 1))] 3.415 g was first eluted and then the more polar isomer B ( (E)-Presumed isomer) [Rf value: 0.35 (silica gel, methylene chloride-
0.789 g of methanol (24: 1)) was eluted. [Isomer A] Light brown crystal Melting point: 144-147 ° C NMR spectrum (90MHz, CDCl ₃ ) δ ppm: 6.34 (1H, s);
6.80-7.10 (2H, m); 7.15-7.50 (6H, m); 9.93 (1H, br.s). Mass spectrum (m / z): 230 (M ⁺ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1685; 161
0; 1595. Elemental analysis (as C ₁₃ H ₁₀ O ₂ S) Calculated: C; 67.80, H; 4.38, S; 13.92. Found: C; 67.71, H; 4.12, N; 13.88. B] Light brown crystal Melting point: 152-155 ° C NMR spectrum (90MHz, CDCl ₃ ) δ ppm: 6.18 (1H, s);
6.95-7.15 (1H, m); 7.15-7.55 (7H, m); 10.66 (1H, br.s). Mass spectrum (m / z): 230 (M ⁺ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1690; 159
Five.

[0255]

Reference Example 2 Diethylphosphono was added to a suspension of (E)-and (Z) -3- (4-pyridyl) sodium cinnamate sodium hydride (5.76 g, content 55%) in tetrahydrofuran (400 ml). Ethyl acetate
(26.92 g) in tetrahydrofuran (100 ml) under ice cooling
The solution was added dropwise at 8-10 ° C over 20 minutes. The reaction mixture was stirred at room temperature for 1 hr, 4-benzoylpyridine (22.00 g) was added, and the mixture was further stirred for 3 hr. The reaction solution was poured into water (300 ml) and extracted with ethyl acetate. The extract was dried over sodium sulfate, the solvent was distilled off, and the residue was subjected to column chromatography using silica gel. By elution with hexane-methylene chloride (3: 1-1: 1), isomer C ((Z) -isomer having lower polarity is estimated) [Rf value: 0.63 (silica gel, methylene chloride-methano- Le (49: 1))] 10.047
When g was first eluted and then eluted with hexane-methylene chloride (1: 1-0: 1), the more polar isomer D (presumed to be the (E) -isomer) [Rf value: 0.55 (silica gel,
16.603 g of methylene chloride-methanol (49: 1)) was eluted. [Isomer C] colorless oil NMR spectrum (90 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.5Hz); 4.07 (2H, q, J = 7.5Hz); 6.48 (1H, s); 7.05-7.55
(7H, m); 8.40-8.90 (2H, m). Mass spectrum (m / z): 253 (M ⁺ ); 208 (M ⁺ -C ₂ H ₅ O). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720. Elemental analysis value (as C ₁₆ H ₁₅ NO ₂ ) Calculated value: C; 75.87, H; 5.97, N; 5.53. Measured value: C; 75.91, H; 6.26, N; 5.48. Isomer D] colorless crystal Melting point: 101-102 ° C NMR spectrum (90MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.5Hz); 4.05 (2H, q, J = 7.5Hz); 6.46 (1H, s); 7.05-7.50
(7H, m); 8.50-8.85 (2H, m). Mass spectrum (m / z): 253 (M ⁺ ); 208 (M ⁺ -C ₂ H ₅ O). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715. elemental analysis (C ₁₆ H ₁₅ as NO ₂₎ calculated: C; 75.87, H; 5.97 , N; 5.53 Found:. C; 75.86, H; 5.86, N; 5.59.

[0256]

Reference Example 3 (E) -3- (4-pyridyl) cinnamic acid (E) -3- (4-pyridyl) methanoate of ethyl cinnamate (3.41 g)
Solution (35 ml) in a 10% aqueous solution of sodium hydroxide (20 m
l) was added and the mixture was stirred at room temperature for 1 hour. The reaction solution is water (50 ml)
Pour in and wash with methylene chloride. Hydrochloric acid was added to the aqueous layer to adjust the pH to 2.8, and the deposited precipitates were collected to obtain the target compound (2.131 g, melting point: 239-241 ° C) as a white powder. NMR spectrum (90MHz, DMSO-d ₆ ) δ ppm: 6.51 (1H,
s); 7.15-7.55 (7H, m); 8.45-8.80 (2H, m). Mass spectrum (m / z): 225 (M ⁺ ); 180 (M ⁺ -COOH). Infrared absorption spectrum ν _max ( Nujoule) cm-1: 169
7; 1625; 1602.

[0257]

[Reference Example 4] Heck reaction of 3,3-diphenylacrylic acid derivative
Synthetic Heck et al. [J.Org.chem., 43 , 2952, (1978
)], An E-acrylic acid ester having a substituent R ¹ at the 3-position and an iodide having a substituent R ² were subjected to a coupling reaction. That is, E having a substituent R ¹ at the 3-position,
- ethyl acrylate (20 mmol), aryl iodide (30 mmol) of the formula R ² -I, triethylamine (4.17 m
l), palladium acetate (0.270 g) and acetonitrile (8
ml) mixture in a sealed tube and placed in an oil bath at 100 ° C for 18
Heated for hours. After allowing to cool, the mixture was diluted with ethyl acetate (30 ml) and washed successively with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and brine. The organic layer was dried and concentrated, and the residue was subjected to flash column chromatography using silica gel (-400 mesh, 400 g) and Rover C column.
It was subjected to medium pressure liquid chromatography using (Si-60 type). Methylene chloride-ether-hexane (1: 1: 5-1:
Elution with a 1: 4) mixture separated the (E) and (Z) isomers of 3,3-disubstituted ethyl acrylate.

In the following description regarding geometrical isomers, the isomer that is first eluted by the above chromatography has been described above.

Further, E- or Z-separated in this way
Ethyl 3,3-diphenylacrylate (4 mmol) in dioxane
Dissolve in a mixture of (12 ml) and methanol (12 ml), 10%
Hydrolysis was carried out by adding an aqueous sodium hydroxide solution (5 ml). After stirring at room temperature for 18 hours, the solvent was distilled off. The residue was diluted with water (20 ml) and washed with ethyl acetate. 10% in water layer
The pH was adjusted to 2 with hydrochloric acid, and the mixture was extracted twice with methylene chloride. The extract was washed with water and dried to obtain 3,3-disubstituted acrylic acid as a solid.

Compounds 4-29, 4-30 and 4- of Reference Example
Toluene was used as an elution solvent in the separation of 33 and 4-34. Separation of compounds 4-93 and 4-94 of the reference example was carried out as follows, since the corresponding ester mixture was not separated by the above chromatography. The E / Z-ester mixture was hydrolyzed as above and the resulting E / Z-acid mixture was washed with methylene chloride. The insoluble material was recrystallized from ether-tetrahydrofuran to obtain the compound of Reference Example 4-93 (presumed to be E-isomer). The methylene chloride solution was concentrated, and the residue was recrystallized from methylene chloride-hexane to obtain the compound of Reference Example 4-94 (presumed to be the Z-isomer).

[0261]

[Chemical formula 22]

[0262]

[Reference Example 4-1] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement = E
Compound yield (%) = 14. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.10 (3H, t, J =
7.32Hz), 3.82 (3H, s), 3.88 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.32 (1H, s), 6.74-6.84 (2H, m), 6.89 (1H, br.s), 7.
16-7.25 (2H, m), 7.34-7.42 (2H, m). Mass spectrum (m / z): 312 (M ⁺ ), 297, 283, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ). cm
-1: 1705, 1595, 1580, 151
0, 1465, 1160, 1135.

[0263]

[Reference Example 4-2] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 21. Melting point (recrystallization solvent) = 93-95 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.92 (3H, s), 4.09 (2H, q, J = 7.32H
z), 6.29 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.82 (1H, dd, J =
8.30,1.95Hz), 6.88 (1H, d, J = 8.30Hz), 7.30-7.14 (5H,
m). Mass spectrum (m / z): 312 (M ⁺ ), 297, 283, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1585, 1515, 1465, 1445, 1160, 1135.

[0264]

[Reference Example 4-3] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = H, arrangement = E
Compound yield (%) = 98. Melting point (recrystallization solvent) = 178-181 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.88 (3H, s), 6.28 (1H, s), 6.75-6.83 (2H, m), 6.86 (1H, b
rs), 7.17-7.25 (2H, m), 7.33-7.43 (3H, m). Mass spectrum (m / z): 284 (M ⁺ ), 269, 267, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1595, 1515, 1260, 1135.

[0265]

[Reference Example 4-4] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = H, arrangement = Z
Compound yield (%) = 99. Melting point (recrystallization solvent) = 162-164 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
3.92 (3H, s), 6.26 (1H, s), 6.75 (1H, d, J = 1.95Hz), 6.80
(1H, dd, J = 8.30,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.27-
7.43 (5H, m). Mass spectrum (m / z): 284 (M ⁺ ), 269, 267, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1605, 1515, 1255, 1135.

[0266]

[Reference Example 4-5] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 19. Melting point (recrystallization solvent) = 119-121 ° C. (Et ₂ O-CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.77 (6H, s), 3.87 (3H, s), 4.05 (2H, q, J = 7.32H
z), 6.32 (1H, s), 6.51 (2H, s), 7.18-7.24 (2H, m), 7.35-
7.41 (3H, m). Mass spectrum (m / z): 342 (M ⁺ ), 327, 313, 299, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
5, 1580, 1500, 1460, 1415, 1160, 1125.

[0267]

[Reference Example 4-6] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 35. Melting point (recrystallization solvent) = 96-98 ° C. (CH ₂ Cl ₂ -Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 3.80 (6H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7.33H
z), 6.32 (1H, s), 6.43 (2H, s), 7.31-7.40 (5H, m). Mass spectrum (m / z): 342 (M ⁺ ), 327, 313, 299, 297. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1585. 1500, 1460, 1410, 1300, 1170, 1125.

[0268]

[Reference Example 4-7] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 100. Melting point (recrystallization solvent) = 202-206 ° C (Et ₂ O-CH ₂ Cl ₂ ) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.76 (6H, s),
3.87 (3H, s), 6.30 (1H, s), 6.49 (2H, s), 7.19-7.25 (2H,
m), 7.35-7.41 (3H, m). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (KBr) cm-1: 2400-3400 (br
oad), 1688, 1610, 1578, 1502, 1241, 1200, 1129.

[0269]

[Reference Example 4-8] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 100. Melting point (recrystallization solvent) = 203-205 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.78 (6H, s),
3.91 (3H, s), 6.30 (1H, s), 6.44 (2H, s), 7.28-7.43 (5H,
m). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1580, 1500, 1460, 1410, 1365,
1125.

[0270]

[Reference Example 4-9] R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 24. Melting point (recrystallization solvent) = 66-68 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.10 (3H, t, J = 7.33Hz), 1.80-1.95 (2H, m), 3.8
1 (3H, s), 3.98 (2H, t, J = 6.84Hz), 4.03 (2H, q, J = 7.33Hz),
6.31 (1H, s), 6.77 (1H, s), 6.78 (1H, s), 6.89 (1H, s),
7.16-7.25 (2H, m), 7.35-7.45 (3H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 269, 253, 226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1600, 1520, 147
0, 1375, 1260, 1160, 114
0.

[0271]

Reference Example 4-10 Compound of R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 37. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.32Hz), 1.15 (3H, t, J = 7.32Hz), 1.80-2.00 (2H, m), 3.7
9 (3H, s), 4.01 (2H, t, J = 6.83Hz), 4.08 (2H, q, J = 7.32Hz),
6.27 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.78 (1H, dd, J = 8.3
0,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.30-7.42 (5H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 269, 253, 226. Red. External absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1515, 1470, 1375, 1260, 1170, 1140.

[0272]

[Reference Example 4-11] R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 94. Melting point (recrystallization solvent) = 147-150 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.75-2.00 (2H, m), 3.79 (3H, s), 3.98 (2H, t, J =
6.84Hz), 6.28 (1H, s), 6.73-6.80 (2H, m), 6.85 (1H, br.
s), 7.15-7.25 (2H, m), 7.33-7.40 (3H, m). Mass spectrum (m / z): 312 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1595, 1580, 1510, 1465, 1260,
1180, 1135.

[0273]

[Reference Example 4-12] R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 93. Melting point (recrystallization solvent) = 139-142 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.80-2.00 (2H, m), 3.79 (3H, s), 4.01 (2H, t, J =
6.84Hz), 6.24 (1H, s), 6.29-6.79 (2H, m), 6.85 (1H, dd, J
= 8.33,1.47Hz), 7.25-7.45 (5H, m). Mass spectrum (m / z): 312 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1575, 1510, 1465, 1445, 1410,
1250, 1130.

[0274]

Reference Example 4-13 Compound of R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = E Yield (%) = 16. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.33Hz), 1.03 (3H, t, J = 7.33Hz), 1.10 (3H, t, J = 7.33Hz),
1.70-1.95 (4H, m), 3.90 (2H, t, J = 6.83Hz), 3.96 (2H, t, J
= 6.83Hz), 4.03 (2H, q, J = 7.33Hz), 6.30 (1H, s), 6.72-6.
80 (2H, m), 6.90 (1H, br, s), 7.15-7.25 (2H, m), 7.30-7.4
5 (3H, m). Mass spectrum (m / z): 368 (M ⁺ ), 326, 323, 284. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 159
5, 1510, 1470, 1370, 1260, 1160, 1130.

[0275]

Reference Example 4-14 Compound with R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 25. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.32Hz), 1.06 (3H, t, J = 7.32Hz), 1.15 (3H, t, J = 7.32Hz),
1.70-1.95 (4H, m), 3.89 (2H, t, J = 6.84Hz), 4.00 (2H, t, J
= 6.84Hz), 4.08 (2H, q, J = 7.32Hz), 6.26 (1H, s), 6.73 (1
H, d, J = 1.95Hz), 6.77 (1H, dd, J = 8.30,1.95Hz), 6.86 (1H,
d, J = 8.30Hz), 7.25-7.40 (5H, m). Mass spectrum (m / z): 368 (M ⁺ ), 326, 323, 284. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1605, 1510, 147
0, 1445, 1370, 1260, 116
0, 1130.

[0276]

[Reference Example 4-15] R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = H, arrangement = E
Compound yield (%) = 92. Melting point (recrystallization solvent) = 102-103 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.32Hz), 1.03 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 3.8
9 (2H, t, J = 6.83Hz), 3.96 (2H, t, J = 6.84Hz), 6.26 (1H, s),
6.74 (1H, dd, J = 8.30,1.96Hz), 6.78 (1H, d, J = 8.30Hz),
6.86 (1H, d, J = 1.96Hz), 7.15-7.25 (2H, m), 7.30-7.40 (3
H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 256, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1595, 1580, 1510, 1425, 1260,
1135.

[0277]

[Reference Example 4-16] Compound with R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = H, configuration = Z Yield (%) = 94. Melting point (recrystallization solvent) = 120-123 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.33Hz), 1.06 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.00 (2H, t, J = 6.84Hz), 6.23 (1H, s),
6.73-6.80 (2H, m), 6.83-6.87 (1H, m), 7.25-7.45 (5H,
m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 256, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1515, 1260, 1135.

[0278]

Reference Example 4-17 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = 83-84 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.84 (3H, s), 3.89 (3H, s), 4.06 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.76 (1H, dd, J = 8.79,1.95Hz), 6.80 (1
H, d, J = 8.79Hz), 6.86 (1H, d, J = 1.95Hz), 7.15 (2H, dm, J =
8.79Hz), 7.36 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 317, 301, 274. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1705, 161
5, 1595, 1580, 1510, 1460, 1370, 1290, 1160, 1135.

[0279]

[Reference Example 4-18] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 22. Melting point (recrystallization solvent) = 67-69 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.91 (3H, s), 6.26 (1H, s), 6.70
(1H, d, J = 1.95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.88 (1
H, d, J = 8.30Hz), 7.12-7.40 (4H, m). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 317, 301, 274. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1590, 1515, 1490, 1460, 1255, 1170, 1135.

[0280]

[Reference Example 4-19] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = H, configuration = E Yield (%) = 85. Melting point (recrystallization solvent) = 164-165 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
3.89 (3H, s), 6.29 (1H, s), 6.76 (1H, dd, J = 8.30,1.95Hz),
6.80 (1H, d, J = 8.30Hz), 6.84 (1H, d, J = 1.95Hz), 7.15 (2
H, dm, J = 8.30Hz), 7.35 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 318 (M ⁺ ), 303, 243. Infrared absorption spectrum ν _max (CHCl ₃ ). cm
-1: 2400-3600 (broad), 169
0, 1610, 1595, 1515, 146
5, 1260, 1175, 1135.

[0281]

[Reference Example 4-20] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 91. Melting point (recrystallization solvent) = 188-190 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
3.92 (3H, s), 6.23 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.78
(1H, dd, J = 8.30,1.95Hz), 6.86 (1H, d, J = 8.30Hz), 7.23 (2
H, dm, J = 8.79Hz), 7.31 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ ), 303, 243. Infrared absorption spectrum ν _max (CHCl ₃ ). cm-1: 2400-3600
(broad), 1690, 1605, 1585, 1515, 1490, 1465, 1415,
1255, 1135.

[0282]

[Reference Example 4-21] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 13. Melting point (recrystallization solvent) = oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J = 7H
z), 3.83 (3H, s), 3.88 (3H, s), 4.06 (2H, q, J = 7Hz), 6.35
(1H, s), 6.75-7.00 (3H, m), 7.00-7.50 (4H, m).

[0283]

Reference Example 4-22 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 20. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J = 7H
z), 3.81 (3H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7Hz), 6.29
(1H, s), 6.70-7.00 (3H, m), 7.10-7.45 (4H, m).

[0284]

[Reference Example 4-23] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 90. Melting point (recrystallization solvent) = 178-181 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
3.89 (3H, s), 6.30 (1H, s), 6.75 (1H, dd, J = 8.30,1.95Hz),
6.80 (1H, d, J = 8.30Hz), 6.85 (1H, d, J = 1.95Hz), 7.10 (1
H, dt, J = 7.81,1.46Hz), 7.20 (1H, t, J = 1.46Hz), 7.31 (1H,
t, J = 7.81Hz), 7.36 (1H, dt, J = 7.81,1.46 Hz). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 303. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1590, 1580, 1510, 1460, 1420,
1255, 1140.

[0285]

[Reference Example 4-24] Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 91. Melting point (recrystallization solvent) = 158-160 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.92 (3H, s), 6.23 (1H, s), 6.73 (1H, d, J = 1.95Hz), 6.78
(1H, dd, J = 8.30,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.15-
7.40 (4H, m). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 303. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1580, 1565, 1515, 1460, 1420,
1255, 1135.

[0286]

[Reference Example 4-25] Compound of R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 4. Melting point (recrystallization solvent) = 82-84 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.39 (3H, s), 3.84 (3H, s), 4.10 (2H, q, J = 7.32H
z), 6.16 (1H, s), 6.82 (1H, dd, J = 8.30,1.46Hz), 6.93 (1
H, dd, J = 8.30,1.46Hz), 7.04 (1H, t, J = 8.30Hz), 7.20 (2H,
dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ C
l), 315, 301, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 16
20, 1600, 1580, 1495, 1475, 1430, 1370, 1260, 117
0.

[0287]

[Reference Example 4-26] Compound in which R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 37. Melting point (recrystallization solvent) = 90-92 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.58 (3H, s), 3.89 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.43 (1H, s), 6.69 (1H, dd, J = 8.30,1.47Hz), 6.95 (1
H, dd, J = 8.30,1.47Hz), 7.08 (1H, t, J = 8.30Hz), 7.28 (4H,
s). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 315, 301, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
5, 1590, 1580, 1495, 1480, 1430, 1370, 1260, 1170.

[0288]

[Reference Example 4-27] Compound with R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = H, configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 129-131 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.39 (3H, s),
3.84 (3H, s), 6.16 (1H, s), 6.79 (1H, dd, J = 8.30,1.47Hz),
6.93 (1H, dd, J = 8.30,1.47Hz), 7.04 (1H, t, J = 8.30Hz),
7.20 (2H, dm, J = 8.79Hz), 7.28 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max ( CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1620, 1600, 1580, 1495, 1475, 1425,
1260.

[0289]

[Reference Example 4-28] Compound in which R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 147 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.57 (3H, s),
3.88 (3H, s), 6.38 (1H, s), 6.67 (1H, dd, J = 7.81,1.46Hz),
6.94 (1H, dd, J = 7.81,1.46Hz), 7.06 (1H, t, J = 7.81Hz),
7.20-7.33 (4H, m). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1590, 1580, 1495, 1480, 1425,
1265.

[0290]

[Reference Example 4-29] R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 13. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (6H, d, J =
6.83Hz), 1.14 (3H, t, J = 7.32Hz), 2.00-2.15 (1H, m), 3.7
2 (2H, d, J = 6.35Hz), 4.05 (2H, q, J = 7.32Hz), 6.30 (1H, s),
6.83 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.20
. (2H, dm, J = 8.79Hz), 7.35 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 358 ( M +, 35 Cl), 313, 302. Infrared absorption spectrum [nu _max (CHCl ₃ ) cm-1: 1710, 160
5, 1515, 1495, 1475, 1375, 1280, 1255, 1170.

[0291]

[Reference Example 4-30] R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 16. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (6H, d, J =
6.83Hz), 1.17 (3H, t, J = 7.32 Hz), 2.00-2.20 (1H, m), 3.
74 (2H, d, J = 6.35Hz), 4.09 (2H, q, J = 7.32Hz), 6.23 (1H,
s), 6.89 (2H, dm, J = 9.28Hz), 7.11 (2H, dm, J = 9.28Hz), 7.
22 (2H, dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 358 (M ⁺ , ³⁵ Cl), 313, 302. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1510, 1490, 1470, 1370, 1285, 1160.

[0292]

[Reference Example 4-31] R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 80. Melting point (recrystallization solvent) = 172-174 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (6H, d, J =
6.83Hz), 1.95-2.20 (1H, m), 3.72 (2H, d, J = 6.84Hz), 6.2
7 (1H, s), 6.83 (2H, dm, J = 8.30Hz), 7.13 (2H, dm, J = 8.30H
z), 7.18 (2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 274, 257. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1590, 1510, 1295, 1250, 1175.

[0293]

[Reference Example 4-32] R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 100. Melting point (recrystallization solvent) = 150-152 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.04 (6H, d, J =
6.35Hz), 2.00-2.20 (1H, m), 3.75 (2H, d, J = 6.34Hz), 6.1
9 (1H, s), 6.87 (2H, dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.79H
z), 7.21 (2H, dm, J = 8.78Hz), 7.30 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 274, 257. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1590, 1515, 1290, 1245, 1175.

[0294]

[Reference Example 4-33] Compound in which R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 19. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.32Hz), 1.14 (3H, t, J = 7.33Hz), 1.74-1.90 (2H, m), 3.9
2 (2H, t, J = 6.83Hz), 4.05 (2H, q, J = 7.33Hz), 6.31 (1H, s),
6.83 (2H, dm, J = 9.28Hz), 7.14 (1H, dm, J = 8.79Hz), 7.20
. (2H, dm, J = 9.28Hz), 7.36 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 344 ( M +, 35 Cl), 302, 299, 272,
257, 230. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1595, 1510, 1370, 1275, 1250, 1160, 1150.

[0295]

[Reference Example 4-34] Compound with R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 27. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.33Hz), 1.16 (3H, t, J = 7.33 Hz), 1.75-1.95 (2H, m), 3.
95 (2H, t, J = 6.84Hz), 4.09 (2H, q, J = 7.33Hz), 6.23 (1H,
s), 6.89 (2H, dm, J = 8.78Hz), 7.12 (2H, dm, J = 8.78Hz), 7.
22 (2H, dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299, 272,
257, 230. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1590, 1510, 1490, 1370, 1290, 1240, 1170, 1150.

[0296]

[Reference Example 4-35] Compound with R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 159-161 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.70-1.90 (2H, m), 3.93 (2H, t, J = 6.84Hz), 6.2
7 (1H, s), 6.83 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.30H
z), 7.19 (2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600 (broad), 169
5, 1600, 1595, 1510, 128
0, 1255, 1180.

[0297]

[Reference Example 4-36] R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement = E
Compound yield (%) = 97. Melting point (recrystallization solvent) = 145-147 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.75-1.90 (2H, m), 3.95 (3H, t, J = 6.35Hz), 6.1
9 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.79H
z), 7.21 (2H, dm, J = 8.79Hz), 7.30 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1590, 1510, 1495, 1290, 1270,
1250, 1175.

[0298]

[Reference Example 4-37] Compound with R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = Et, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = 133-135 ° C. (Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.78 (6H, s), 3.87 (3H, s), 4.07 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.48 (2H, s), 7.03-7.13 (2H, m), 7.17-
7.25 (2H, m). Mass spectrum (m / z): 360 (M ⁺ ), 345, 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1580, 1505, 1465, 1415, 1355, 1165, 1155, 1130.

[0299]

[Reference Example 4-38] Compound with R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = Et, configuration = Z Yield (%) = 37. Melting point (recrystallization solvent) = 62-64 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 3.80 (6H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7.33H
z), 6.26 (1H, s), 6.41 (2H, s), 6.98-7.08 (2H, m), 7.27-
7.36 (2H, m). Mass spectrum (m / z): 360 (M ⁺ ), 345, 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1585, 1505, 1465, 1415, 1370, 1310, 1160, 1130.

[0300]

[Reference Example 4-39] Compound with R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = H, configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 201-204 ° C. (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.78 (6H, s),
3.87 (3H, s), 6.28 (1H, s), 6.46 (2H, s), 7.02-7.12 (2H,
m), 7.12-7.25 (2H, m). Mass spectrum (m / z): 332 (M ⁺ ), 317. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1580, 1505, 1130.

[0301]

Reference Example 4-40 Compound with R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = H, Configuration = Z Yield (%) = 100. Melting point (recrystallization solvent) = 187-189 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.79 (6H, s),
3.91 (3H, s), 6.24 (1H, s), 6.42 (2H, s), 6.99-7.09 (2H,
m), 7.27-7.35 (2H, m). Mass spectrum (m / z): 332 (M ⁺ ), 317. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1585, 1505, 1415, 1125.

[0302]

[Reference Example 4-41] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 20. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.32Hz), 3.826 (3H, s), 3.848 (3H, s), 3.89 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.23 (1H, s), 6.77-6.89 (3H, m), 6.91
(2H, dm, J = 8.78Hz), 7.16 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 342 (M ⁺ ), 313, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
5, 1580, 1510, 1465, 1290, 1165, 1135.

[0303]

[Reference Example 4-42] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 30. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.85 (3H, s), 3.92 (3H, s), 4.07
(2H, q, J = 7.32Hz), 6.24 (1H, s), 6.71 (1H, d, J = 1.95Hz),
6.77-6.94 (4H, m), 7.26 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 342 (M ⁺ ), 313, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1705, 160
0, 1510, 1465, 1250, 1170, 1135.

[0304]

[Reference Example 4-43] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 91. Mp (recrystallization _{solvent) = 161-163 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.82 (3H, s),
3.85 (3H, s), 3.89 (3H, s), 6.20 (1H, s), 6.74-6.82 (2H,
m), 6.84 (1H, br.s), 6.89 (2H, dm, J = 8.79Hz), 7.17 (2H, d
m, J = 8.79Hz). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 2400-3600 (broad), 168
5, 1605, 1595, 1510, 146
5, 1290, 1245, 1170, 113
5.

[0305]

[Reference Example 4-44] R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = H,
Configuration = Compound of Z Yield (%) = 97. Melting point (recrystallization solvent) = 149-152 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.83 (3H, s), 3.92 (3H, s), 6.21 (1H, s), 6.74 (1H, d, J = 1.
95Hz), 6.80 (1H, dd, J = 8.30,1.95Hz), 6.82-6.93 (3H, m),
7.14-7.29 (2H, m). Mass spectrum (m / z): 314 (M ⁺ ), 299, 270. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1515, 1465, 1255, 1175, 1135.

[0306]

[Reference Example 4-45] R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 62. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J = 7H
z), 3.80 (3H, s), 4.06 (2H, q, J = 7Hz), 6.35 (1H, s), 6.8-
7.4 (7H, m).

[0307]

[Reference Example 4-46] R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 23. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J = 7H
z), 3.84 (3H, s), 4.06 (2H, q, J = 7Hz), 6.23 (1H, s), 6.7-
7.5 (7H, m).

[0308]

[Reference Example 4-47] R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 84. Melting point (recrystallization solvent) = 181-184 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CD ₃ OD) δ ppm: 3.80 (3H, s),
6.36 (1H, s), 6.91 (2H, dm, J = 9.28Hz), 7.08 (1H, dd, J = 8.3
0,1.95Hz), 7.23 (2H, dm, J = 9.28Hz), 7.31 (1H, d, J = 1.95H
z), 7.51 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared absorption spectrum ν _max (KBr) cm-1: 2300 -3400 (br
oad), 1692, 1597, 1585, 1510, 1288, 1254, 1214, 11
78, 1162.

[0309]

[Reference Example 4-48] R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 95. Melting point (recrystallization solvent) = 193-196 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CD ₃ OD) δ ppm: 3.83 (3H, s),
6.30 (1H, s), 6.93 (2H, dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.7
9Hz), 7.23 (1H, dd, J = 8.30,1.95Hz), 7.38 (1H, d, J = 1.95H
z), 7.50 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared absorption spectrum ν _max (KBr) cm-1: 2300 -3400 (br
oad), 1688, 1662, 1602, 1512, 1407, 1281, 1253, 12
07, 1177.

[0310]

[Reference Example 4-49] Compound with R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 13. Melting point (recrystallization solvent) = 72-74 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.08 (3H, t, J =
7.32Hz), 3.84 (3H, s), 3.89 (3H, s), 4.03 (2H, q, J = 7.32H
z), 6.37 (1H, s), 6.72 (1H, dd, J = 8.30,1.96Hz), 6.80 (1
H, d, J = 8.30Hz), 6.87 (1H, d, J = 1.96Hz), 7.35-7.70 (4H,
m). Mass spectrum (m / z): 380 (M ⁺ ), 361, 335. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1595, 1515, 146
0, 1370.

[0311]

Reference Example 4-50 Compound with R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 16. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.18 (3H, t, J =
7.32Hz), 3.82 (3H, s), 3.93 (3H, s), 4.11 (2H, q, J = 7.32H
z), 6.30 (1H, s), 6.71 (1H, d, J = 1.95Hz), 6.81 (1H, dd, J =
8.30,1.96Hz), 6.89 (1H, d, J = 8.30Hz), 7.40-7.50 (2H,
m), 7.57-7.68 (2 H, m). Mass spectrum (m / z): 380 (M ⁺ ), 361, 335. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1515, 1460, 1370, 1325.

[0312]

[Reference Example 4-51] Compound in which R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 100. Melting point (recrystallization solvent) = 142-144 ° C (CH ₂ Cl ₂ -hexane)

[0313]

[Reference Example 4-52] Compound in which R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = H, and configuration = Z Yield (%) = 100. Mp (recrystallization _{solvent) = 140-143 ℃ (CH 2 Cl} 2 -hexane)

[0314]

[Reference Example 4-53] Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 21. Melting point (recrystallization solvent) = 75-77 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.32Hz), 2.39 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 4.06
(2H, q, J = 7.32Hz), 6.27 (1H, s), 6.77 (1H, d, J = 8.30Hz),
6.81 (1H, dd, J = 8.30,1.95Hz), 6.89 (1H, d, J = 1.95Hz), 7.
01-7.22 (4H, m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1580, 1510, 1465, 1440, 1370, 1290, 1250, 1160,
1130.

[0315]

[Reference Example 4-54] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 38. Melting point (recrystallization solvent) = 69-70 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 2.36 (3H, s), 3.81 (3H, s), 3.91 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.27 (1H, s), 6.72 (1H, d, J = 1.95Hz),
6.81 (1H, dd, J = 7.81,1.95Hz), 6.88 (1H, d, J = 7.81Hz), 7.
13 (2H, dm, J = 8.30Hz), 7.21 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1510, 1465, 1415, 1370, 1250, 1160, 1135.

[0316]

[Reference Example 4-55] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 97. Melting point (recrystallization solvent) = 167-170 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.39 (3H, s),
3.88 (3H, s), 3.92 (3H, s), 6.24 (1H, s), 7.79 (1H, m), 6.
86 (1H, br.s), 7.08-7.22 (4H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400- 3600
(broad), 1690, 1600, 1580, 1510, 1465, 1440, 1420,
1325, 1290, 1250, 1175, 1135.

[0317]

[Reference Example 4-56] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 185-188 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.36 (3H, s),
3.80 (3H, s), 3.92 (3H, s), 6.24 (1H, s), 6.75 (1H, d, J = 1.
95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.86 (1H, d, J = 8.30
Hz), 7.10-7.23 (4H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1605, 1515, 1465, 1420, 1260, 1180,
1140.

[0318]

[Reference Example 4-57] Compound with R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 52. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 2.33 (3H, s), 4.08 (2H, q, J = 7.32Hz), 6.36 (1H,
s), 7.03-7.13 (3H, m), 7.15-7.23 (2H, m), 7.30 (1H, d, J =
1.95Hz), 7.46 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 334 (M ⁺ , ³⁵ Cl), 305, 289, 262. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1715, 162
0, 1470, 1370, 1280, 1170, 1150.

[0319]

[Reference Example 4-58] Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 19. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.11 (3H, t, J =
7.32Hz), 2.35 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.30 (1H,
s), 6.95-7.05 (2H, m), 7.12 (1H, dd, J = 8.79,1.95Hz), 7.
15-7.32 (2H, m), 7.379 (1H, d, J = 1.95Hz), 7.385 (1H, d, J =
8.79Hz). Mass spectrum (m / z): 334 (M ⁺ , ³⁵ Cl), 305, 289, 262. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
0, 1470, 1380, 1370, 1350, 1280, 1250, 1175.

[0320]

[Reference Example 4-59] Compound with R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 95. Melting point (recrystallization solvent) = 163-165 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
6.33 (1H, s), 7.00-7.10 (3H, m), 7.18-7.28 (2H, m), 7.29
(1H, d, J = 1.95Hz), 7.45 (1H, d, J = 7.81Hz). Mass spectrum (m / z): 306 (M ⁺ , ³⁵ Cl), 291, 261. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1585, 1475, 1290, 1125.

[0321]

[Reference Example 4-60] Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 152-154 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
6.26 (1H, s), 6.94-7.03 (2H, m), 7.09 (1H, dd, J = 8.30,1.9
6Hz), 7.18-7.32 (2H, m), 7.35 (1H, d, J = 1.96Hz), 7.39 (1
H, d, J = 8.30Hz). Mass spectrum (m / z): 306 (M ⁺ , ³⁵ Cl), 291, 261. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1470, 1410, 1285, 1180, 1130.

[0322]

[Reference Example 4-61] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 23. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.11 (3H, t, J =
7.32Hz), 2.36 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 4.04
(2H, q, J = 7.32Hz), 6.29 (1H, s), 6.75-6.84 (2H, m), 6.90
(1H, br.s), 6.94-7.05 (2H, m), 7.15-7.31 (2H, m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1515, 1470, 1445, 1330, 1295, 1255, 1160,
1145, 1130.

[0323]

[Reference Example 4-62] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 33. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.33Hz), 2.33 (3H, s), 3.81 (3H, s), 3.92 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.72 (1H, d, J = 1.96Hz), 6.81 (1H, dd, J
= 8.30,1.96Hz), 6.88 (1H, d, J = 8.30Hz), 7.07-7.26 (4H,
m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1590, 1520, 1470, 1260, 1180, 1160, 1145, 1135.

[0324]

[Reference Example 4-63] Compound with R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 140-143 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.35 (3H, s),
3.82 (3H, s), 3.89 (3H, s), 6.27 (1H, s), 6.74-6.83 (2H,
m), 6.87 (1H, br.s), 6.99-7.06 (2H, m), 7.15-7.31 (2H,
m). Mass spectrum (m / z): 298 (M ⁺ ), 283, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1580, 1515, 1470, 1260, 1170,
1145, 1130.

[0325]

[Reference Example 4-64] Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 148-150 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
3.81 (3H, s), 3.92 (3H, s), 6.24 (2H, s), 6.75 (1H, d, J = 1.
96Hz), 6.80 (1H, dd, J = 8.30,1.96Hz), 6.87 (1H, d, J = 8.30
Hz), 7.05-7.14 (2H, m), 7.16-7.24 (2H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 2400-3600
(broad), 1690, 1605, 1585, 1515, 1450, 1440, 1420,
1255, 1175, 1135.

[0326]

[Reference Example 4-65] Compound with R ¹ = 2-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 81. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.10 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.03 (2H, q, J = 7.33Hz), 6.48 (1H,
s), 6.85 (2H, dm, J = 9.28Hz), 7.11-7.20 (1H, m), 7.26 (2
H, dm, J = 9.28Hz), 7.26-7.37 (2H, m), 7.40-7.50 (1H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 281, 271, 253 Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1575, 1515, 1465, 1370, 1355, 1280, 1255,
1160.

[0327]

[Reference Example 4-66] Compound in which R ¹ = 2-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 85. Melting point (recrystallization solvent) = 162-164 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
6.44 (1H, s), 6.84 (2H, dm, J = 8.79Hz), 7.09-7.16 (1H,
m), 7.24 (2H, dm, J = 8.79Hz), 7.26-7.35 (2H, m), 7.37-7.
46 (1H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 253, 238. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1700, 1620, 1605, 1595, 1575, 1515, 1425,
1290, 1260, 1180, 1160.

[0328]

[Reference Example 4-67] Compound with R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 8. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.13 (3H, t, J =
7.32Hz), 3.78 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.37 (1H,
s), 6.81 (1H, t, J = 1.96Hz), 6.86 (1H, ddd, J = 8.31,1.96,
0.98Hz), 6.91 (1H, ddd, J = 8.31,1.96,0.98Hz), 7.10 (1H,
dt, J = 7.81,1.95Hz), 7.20 (1H, t, J = 1.95Hz), 7.25 (1H, t,
J = 7.81Hz), 7.31 (1H, t, J = 7.81Hz), 7.35 (1H, dt, J = 7.81,
Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 243,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 162
0, 1600, 1580, 1490, 1470, 1435, 1370, 1350, 1290,
1280, 1170.

[0329]

[Reference Example 4-68] Compound in which R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 18. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.32Hz), 3.79 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.72 (1H, dd, J = 2.44,1.46Hz), 6.79 (1H, dt, J = 7.81,
1.46Hz), 6.93 (1H, ddd, J = 8.30,2.44,1.46Hz), 7.18 (1H,
dt, J = 7.32,1.46Hz), 7.22-7.36 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 243,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
0, 1590, 1580, 1570, 1490, 1470, 1430, 1370, 1350,
1290, 1260, 1170.

[0330]

[Reference Example 4-69] Compound with R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 115-117 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.78 (3H, s),
6.35 (1H, s), 6.78 (1H, t, J = 1.47Hz), 6.84 (1H, dm, J = 7.81
Hz), 6.93 (1H, dm, J = 7.81Hz), 7.10 (1H, dt, J = 7.32,1.47H
z), 7.25 (1H, t, J = 7.81Hz), 7.30 (1H, t, J = 7.32Hz), 7.36
(1H, dt, J = 7.33,1.47 Hz). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400- 3600
(broad), 1695, 1620, 1600, 1580, 1490, 1435, 1410,
1345, 1290, 1150.

[0331]

[Reference Example 4-70] Compound with R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 96. Melting point (recrystallization solvent) = 140-142 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.79 (3H, s),
6.30 (1H, s), 6.72 (1H, dd, J = 2.44,1.47Hz), 6.78 (1H, dm,
J = 7.32Hz), 6.93 (1H, ddd, J = 8.30,2.44,0.97Hz), 7.16 (1
H, dt, J = 7.81,1.47Hz), 7.23-7.38 (4H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1600, 1590, 1570, 1490, 1470,
1460, 1430, 1350, 1285.

[0332]

[Reference Example 4-71] Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 10. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.32 (1H,
s), 6.85 (2H, dm, J = 9.28Hz), 7.09 (1H, dt, J = 7.30,1.96H
z), 7.18-7.39 (5H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ C
l), 287, 271, 244, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 16
05, 1600, 1570, 1515, 1465, 1420, 1370, 1350, 129
0, 1275, 1255, 1170, 1155.

[0333]

[Reference Example 4-72] Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.25 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
15-7.36 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 244,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1570, 1515, 1470, 1370, 1355, 1295, 1250, 1175.

[0334]

[Reference Example 4-73] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 94. Melting point (recrystallization solvent) = 158-160 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 9.28Hz), 7.09 (2H, dt, J = 7.3
0,1.46Hz), 7.16-7.38 (5H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1605, 1590, 1570, 1515, 1425, 1285,
1255, 1180.

[0335]

[Reference Example 4-74] Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 119-120 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.21 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.7
9Hz), 7.12-7.38 (4H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1570, 1515, 1420, 1295, 1250,
1180.

[0336]

[Reference Example 4-75] Compound in which R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 4. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.32Hz), 1.16 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.9
3 (2H, t, J = 6.84Hz), 4.07 (2H, q, J = 7.32Hz), 6.32 (1H, s),
6.84 (2H, dm, J = 8.79Hz), 7.06 (1H, dd, J = 8.30,1.95Hz),
7.20 (2H, dm, J = 8.79Hz), 7.29 (1H, d, J = 1.95Hz), 7.45 (1
H, d, J = 8.30Hz) .Mass spectrum (m / z): 378 (M ⁺ , ³⁵ Cl), 336, 333, 308,
305, 291, 264.

[0337]

[Reference Example 4-76] Compound in which R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 5. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.32Hz), 1.17 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.35Hz), 4.09 (2H, q, J = 7.32Hz), 6.22 (1H, s),
6.90 (2H, dm, J = 8.79Hz), 7.11 (2H, dm, J = 8.79Hz), 7.13
(1H, dd, J = 8.30,1.96Hz), 7.38 (1H, d, J = 1.96Hz), 7.39 (1
H, d, J = 8.30Hz) .Mass spectrum (m / z): 378 (M ⁺ , ³⁵ Cl), 336, 333, 308,
305, 291, 264. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 163
0, 1515, 1470, 1390, 1370, 1350, 1290, 1280, 1245,
1170.

[0338]

[Reference Example 4-77] Compound with R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Mp (recrystallization _{solvent) = 161-163 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.93 (2H, t, J = 6.84Hz), 6.2
9 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 7.06 (1H, dd, J = 8.30,
1.95Hz), 7.19 (2H, dm, J = 8.79Hz), 7.28 (1H, d, J = 1.95H
z), 7.45 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 308, 291, 263. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 2400-3600
(broad), 1695, 1605, 1590, 1515, 1475, 1285, 1255,
1180.

[0339]

[Reference Example 4-78] Compound with R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = H, configuration = E Yield (%) = 85. Melting point (recrystallization solvent) = 155-157 ° C (CH ₂ Cl ₂ -hexane)

[0340]

[Reference Example 4-79] R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 21. Melting point (recrystallization solvent) = 89-91 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.33Hz), 1.46 (3H, t, J = 7.33Hz), 3.81 (3H, s), 4.03 (2H,
q, J = 7.33Hz), 4.10 (2H, q, J = 7.33Hz), 6.31 (1H, s), 6.77
(2H, br.s), 6.90 (1H, br.s), 7.16-7.25 (2H, m), 7.32-7.
41 (3H, m). Mass spectrum (m / z): 326 (M ⁺ , ³⁵ Cl), 297, 281, 253,
226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
5, 1600, 1580, 1515, 1480, 1470, 1370, 1320, 1290,
1250, 1160, 1135.

[0341]

[Reference Example 4-80] R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 32. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J =
7.32Hz), 1.49 (3H, t, J = 7.32Hz), 3.80 (3H, s), 4.08 (2H,
q, J = 7.32Hz), 4.14 (2H, q, J = 7.32Hz), 6.28 (1H, s), 6.73
(1H, d, J = 1.95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.87 (1
H, d, J = 8.30Hz), 7.29-7.40 (5H, m). Mass spectrum (m / z): 326 (M ⁺ , ³⁵ Cl), 297, 281, 253,
226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1580, 1515, 1480, 1470, 1450, 1410, 1370, 1355,
1320, 1250, 1160, 1130.

[0342]

[Reference Example 4-81] R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 93. Melting point (recrystallization solvent) = 200-202 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 1.
45 (3H, t, J = 6.96Hz), 3.80 (3H, s), 4.11 (2H, q, J = 6.96H
z), 6.32 (1H, s), 6.80 (1H, dd, J = 8.43,1.83Hz), 6.84 (1
H, d, J = 8.43Hz), 6.88 (1H, d, J = 1.83Hz), 7.18-7.27 (2H,
m), 7.32-7.42 (3H, m). Mass spectrum (m / z): 298 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (KBr) cm-1: 2400-3600 (br
oad), 1692, 1660, 1605, 1587, 1514, 1479, 1421, 14
02, 1324, 1297, 1274, 1255, 1204, 1137.

[0343]

[Reference Example 4-82] R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 90. Melting point (recrystallization solvent) = 133-135 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.49 (3H, t, J =
7.33Hz), 3.80 (3H, s), 4.14 (2H, q, J = 7.32Hz), 6.25 (1H,
s), 6.72-6.86 (3H, m), 7.27-7.43 (5H, m). Mass spectrum (m / z): 298 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) Cm
-1: 2400-3600 (broad), 169
0, 1605, 1580, 1515, 147
0, 1450, 1415, 1255, 113
5.

[0344]

[Reference Example 4-83] Compound in which R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = Et, configuration = E Yield (%) = 21. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.43-1.54 (2
H, m), 1.78-1.86 (2H, m), 3.80 (3H, s), 4.02 (2H, t, J = 6.84
Hz), 4.03 (2H, q, J = 7.33Hz), 6.31 (1H, s), 6.77 (2H, br.
s), 6.79 (1H, br.s), 7.17-7.24 (2H, m), 7.34-7.41 (3H,
m). Mass spectrum (m / z): 354 (M ⁺ ), 309, 298, 269, 226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 169
0, 1610, 1595, 1580, 1510, 1465, 1370, 1290, 1270,
1250, 1160, 1135.

[0345]

[Reference Example 4-84] R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 47. Melting point (recrystallization solvent) = oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (3H, t, J = 7H
z), 1.13 (3H, t, J = 7Hz), 1.30-2.20 (4H, m), 3.78 (3H, s),
4.02 (2H, t, J = 7Hz), 4.10 (2H, q, J = 7Hz), 6.30 (1H, s), 6.
70-7.05 (3H, m).

[0346]

[Reference Example 4-85] R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 92. Melting point (recrystallization solvent) = 140-435 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 0.97 (3H, t, J =
7.33Hz), 1.40-1.60 (2H, m), 1.75-1.90 (2H, m), 3.79 (3
H, s), 4.02 (2H, t, J = 6.84Hz), 6.28 (1H, s), 6.75 (1H, dd,
J = 8.78,1.47Hz), 6.78 (1H, d, J = 8.78Hz), 6.85 (1H, d, J =
1.47Hz), 7.17-7.24 (2H, m), 7.30-7.40 (3H, m). Mass spectrum (m / z): 326 (M ⁺ ), 2
70, 253, 237. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-360
0 (broad), 1690, 1610, 1595, 1580, 1510, 1500, 147
0, 1420, 1320, 1250, 1135.

[0347]

[Reference Example 4-86] R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 50. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.32Hz), 2.66 (2H, q, J = 7.32Hz),
4.08 (2H, q, J = 7.32Hz), 6.37 (1H, s), 7.06 (1H, dd, J = 8.3
0,1.95Hz), 7.12-7.24 (4H, m), 7.30 (1H, d, J = 1.95Hz),
7.46 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 348 (M ⁺ , ³⁵ Cl), 319, 303, 276. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710 , 162
0, 1610, 1470, 1370, 1275, 1170, 1160.

[0348]

[Reference Example 4-87] R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 14. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.10 (3H, t, J = 7H
z), 1.27 (3H, t, J = 7Hz), 2.70 (2H, q, J = 7Hz), 4.05 (2H, q, J
= 7Hz), 6.27 (1H, s), 6.98-7.60 (7H, m).

[0349]

[Reference Example 4-88] R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 94. Melting point (recrystallization solvent) = 172-174 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.24 (3H, t, J =
7.32Hz), 2.66 (2H, q, J = 7.32Hz), 6.35 (1H, s), 7.06 (1H,
dd, J = 7.82,1.95Hz), 7.12-7.24 (4H, m), 7.29 (1H, d, J = 1.
95Hz), 7.45 (1H, d, J = 7.82Hz). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 305, 291, 275. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 2400-3600
(broad), 1690, 1620, 1605, 1470, 1280, 1180, 1160,
1120.

[0350]

[Reference Example 4-89] Compound in which R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = Et, configuration = Z Yield (%) = 35. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.33Hz), 1.67 (3H, t, J = 7.33Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.60Hz), 4.09 (2H, q, J = 7.33Hz), 6.26 (1H, s),
6.89 (2H, dm, J = 8.80Hz), 7.14 (2H, dm, J = 8.80Hz), 7.26-
7.40 (5H, m). Mass spectrum (m / z): 310 (M ⁺ ), 268, 265, 238, 223,
196. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1370, 1290, 1260, 1240, 1170.

[0351]

[Reference Example 4-90] Compound with R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = Et, configuration = E Yield (%) = 35. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.33Hz), 1.10 (3H, t, J = 7.33Hz), 1.75-1.90 (2H, m), 3.9
2 (2H, t, J = 6.84Hz), 4.03 (2H, q, J = 7.33Hz), 6.30 (1H, s),
6.82 (2H, dm, J = 9.27Hz), 7.15-7.28 (2H, m), 7.23 (2H, d
m, J = 9.27Hz), 7.28-7.43 (3H, m). Mass spectrum (m / z): 310 (M ⁺ ), 268, 265, 238, 223,
196. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1595, 1575, 1510, 1370, 1250, 1160, 1150.

[0352]

[Reference Example 4-91] Compound with R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = H, configuration = Z Yield (%) = 93. Melting point (recrystallization solvent) = 183-185 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.75-1.90 (2H, m), 3.95 (2H, t, J = 6.84Hz), 6.2
3 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.79H
z), 7.26-7.42 (5H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240, 223, 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1515, 1290, 1280, 1250, 1175.

[0353]

[Reference Example 4-92] Compound in which R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = H, configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 138-140 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7Hz), 1.45-2.20 (2H, m), 3.90 (2H, q, J = 7Hz), 6.27 (1H,
s), 6.83 (2H, dm, J = 9Hz), 7.05-7.60 (7H, m), 10.00 (1H, b
rm).

[0354]

[Reference Example 4-93] R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, R ¹¹ =
Compound with H, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = 222-224 ° C. (Et ₂ O-tetrahydrofuran) NMR spectrum (60 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 5.
99 (2H, s), 6.29 (1H, s), 6.79 (3H, s), 7.05-7.60 (5H, m).

[0355]

[Reference Example 4-94] R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, R ¹¹ =
Compound with H, configuration = Z Yield (%) = 51. Melting point (recrystallization solvent) = 141-143 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 6.00 (2H, s),
6.26 (1H, s), 6.72-6.96 (3H, m), 7.15-7.55 (5H, m).

[0356]

[Reference Example 4-95] Compound in which R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 22. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.32Hz), 1.11 (3H, t, J = 7.32Hz), 1.80-1.95 (2H, m), 2.3
5 (3H, s), 3.81 (3H, s), 3.98 (2H, t, J = 6.84Hz), 4.04 (2H,
q, J = 7.32Hz), 6.29 (1H, s), 6.72-6.86 (2H, m), 6.90 (1H,
br.s), 6.98-7.05 (2H, m), 7.15-7.24 (1H, m), 7.30-7.42
(1H, m). Mass spectrum (m / z): 354 (M ⁺ ), 312, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1510, 1485, 1370, 1290, 1260, 1160, 1145,
1130.

[0357]

[Reference Example 4-96] Compound with R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 40. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.32Hz), 1.15 (3H, t, J = 7.32Hz), 1.80-1.95 (2H, m), 2.3
2 (3H, s), 3.80 (3H, s), 4.02 (2H, t, J = 6.84Hz), 4.08 (2H,
q, J = 7.32Hz), 6.26 (1H, s), 6.72 (1H, d, J = 1.96Hz), 6.78
(1H, dd, J = 7.82,1.96Hz), 6.87 (1H, d, J = 7.82Hz), 7.06-
7.25 (4H, m). Mass spectrum (m / z): 354 (M ⁺ ), 312, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1515, 1465, 1370, 1250, 1180, 1160, 1130.

[0358]

Reference Example 4-97 Compound with R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, Configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 123-126 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.75-1.95 (2H, m), 2.34 (3H, s), 3.80 (3H, s),
3.98 (2H, t, J = 6.84Hz), 6.26 (1H, s), 6.74 (1H, dd, J = 8.7
9,1.95Hz), 6.78 (1H, d, J = 8.79Hz), 6.86 (1H, d, J = 1.95H
z), 6.98-7.05 (2H, m), 7.14-7.30 (2H, m). Mass spectrum (m / z): 326 (M ⁺ ), 284, 267, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1595, 1580, 1515, 1470, 1260, 1175,
1145, 1130.

[0359]

[Reference Example 4-98] Compound with R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 132-135 ° C (CH ₂ Cl ₂ -hexane)

[0360]

[Reference Example 4-99] Compound of R ¹ = 3-CH ₃ Ph, R ² = 3-CH ₃ Ph, R ¹¹ = Et Yield (%) = 78. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.11 (3H, t, J =
7.32Hz), 2.32 (3H, s), 2.35 (3H, s), 4.03 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.98-7.30 (8H, m). Mass spectrum (m / z): 280 (M ⁺ ), 265, 251, 235, 208. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1600, 1580, 1370, 1350, 1280, 1190, 1160.

[0361]

Reference Example 4-100 Compound of R ¹ = 3-CH ₃ Ph, R ² = 3-CH ₃ Ph, R ¹¹ = H Yield (%) = 94. Melting point (recrystallization solvent) = 133-135 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.32 (3H, s),
2.34 (3H, s), 6.28 (1H, s), 6.98-7.12 (4H, m), 7.14-7.30
(4H, m). Mass spectrum (m / z): 252 (M ⁺ ), 237, 235, 207. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1615, 1600, 1580, 1430, 1285, 1170.

[0362]

Reference Example 4-101 Compound with R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 10. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (3H, t, J =
7.33Hz), 1.12 (3H, t, J = 7.33Hz), 1.70-1.85 (2H, m), 3.8
8 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.33Hz), 6.37 (1H, s),
6.80-6.86 (2H, m), 6.90 (1H, ddd, J = 8.30,2.44,0.97Hz),
7.10 (1H, ddd, J = 6.84,1.47,1.47Hz), 7.19-7.38 (4H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1600, 1580, 1485, 1475, 1440, 1370, 1350, 1290,
1170.

[0363]

Reference Example 4-102 Compound with R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 18. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (3H, t, J =
7.33Hz), 1.12 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.33Hz), 6.32 (1H, s),
6.71 (1H, m), 6.77 (1H, ddd, J = 7.81,1.46,0.98Hz), 6.92
(1H, ddd, J = 8.30,2.93,0.98Hz), 7.16-7.35 (5H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1600, 1580, 157
0, 1475, 1440, 1370, 135
0, 1280, 1260, 1170, 103
0.

[0364]

[Reference Example 4-103] R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = H, arrangement = Z
Compound yield (%) = 94. Melting point (recrystallization solvent) = 118-120 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.88 (2H, t, J = 6.84Hz), 6.3
4 (1H, s), 6.77-6.85 (2H, m), 6.92 (1H, ddd, J = 7.32,2.44,
0.98Hz), 7.10 (1H, ddd, J = 7.31,1.46,1.46Hz), 7.17-7.3
8 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1695, 162
0, 1600, 1580, 1490, 1480, 1440, 1410, 1350, 1290,
1150.

[0365]

Reference Example 4-104 Compound in which R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 10. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7.32Hz), 1.12 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.84Hz), 4.04 (2H, q, J = 7.32Hz), 6.31 (1H, s),
6.84 (2H, dm, J = 8.79Hz), 7.09 (1H, ddd, J = 6.84,1.95,1.9
5Hz), 7.17-7.20 (1H, m), 7.21 (2H, dm, J = 8.79Hz), 7.28-
7.40 (2H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1590, 1570, 1510, 1470, 1370, 1275, 1255, 1170,
1155.

[0366]

[Reference Example 4-105] Compound in which R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.05 (3H, t, J =
7.32Hz), 1.17 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.84Hz), 4.09 (2H, q, J = 7.32Hz), 6.24 (1H, s),
6.89 (2H, dm, J = 8.79Hz), 7.12 (1H, dm, J = 8.79Hz), 7.17
(1H, dd, J = 7.81,1.95,1.95Hz), 7.25 (1H, dd, J = 7.81,7.8
1Hz), 7.28 (1H, dd, J = 1.95,1.95Hz), 7.33 (1H, ddd, J = 7.8
1,1.95,1.95Hz). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1470, 1290, 1240, 1170.

[0367]

[Reference Example 4-106] Compound in which R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 92. Melting point (recrystallization solvent) = 174.5-176.5 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.74-1.90 (2H, m), 3.93 (2H, t, J = 6.83Hz), 6.2
9 (1H, s), 6.84 (2H, dm, J = 9.28Hz), 7.09 (1H, ddd, J = 7.33,
1.95,1.95Hz), 7.16-7.20 (1H, m), 7.20 (2H, dm, J = 9.28H
z), 7.27-7.38 (2H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (KBr) cm-1: 3400- 2400, 1
665, 1600, 1585, 1510, 1305, 1260, 1245, 1180.

[0368]

[Reference Example 4-107] Compound in which R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 147-149 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 3.96 (2H, t, J = 6.34Hz), 6.2
0 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79H
z), 7.14-7.19 (1H, m), 7.23-7.38 (3H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1610, 1570, 1515, 1290, 1250, 1180.

[0369]

[Reference Example 4-108] Compound with R ¹ = 2-ClPh, R ² = 3-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 63. Melting point (recrystallization solvent) = 82-84 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.32Hz), 3.78 (3H, s), 4.04 (2H, q, J = 7.32Hz), 6.54 (1H,
s), 6.84-6.94 (3H, m), 7.14-7.19 (1H, m), 7.21-7.36 (3
H, m), 7.40-7.48 (1H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 281, 271, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1 : 1715, 161
5, 1600, 1580, 1490, 1470, 1435, 1370, 1350, 1290,
1170, 1050, 1035.

[0370]

[Reference Example 4-109] Compound with R ¹ = 2-ClPh, R ² = 3-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 140-142 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.77 (3H, s),
6.51 (1H, s), 6.83 (1H, dd, J = 1.95,1.95Hz), 6.86-6.94 (2
H, m), 7.11-7.18 (1H, m), 7.21-7.35 (3H, m), 7.38-7.46
(1H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1695, 1625, 1600, 1580, 1490, 1470, 1430, 1290,
1050.

[0371]

[Reference Example 4-110] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = Et, configuration = Z Yield (%) = 9. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.31 (1H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.14 (1H, ddd, J = 7.81,1.47,
1.47Hz), 7.22 (2H, dm, J = 8.79Hz), 7.25 (1H, ddd, J = 7.81,
7.81,1.47Hz), 7.35 (1H, dd, J = 1.47,1.47Hz), 7.51 (1H, d
dd, J = 7.81,1.47,1.47Hz). Mass spectrum (m / z): 360 (M ⁺ , ⁷⁹ Br), 333, 315, 288. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710 , 160
0, 1510, 1370, 1290, 1270, 1250, 1165, 1025, 830.

[0372]

Reference Example 4-111 Compound with R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = Et, Configuration = E Yield (%) = 12. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.24 (1H,
s), 6.90 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
18-7.24 (2H, m), 7.43-7.52 (2H, m). Mass spectrum (m / z): 360 (M ⁺ , ⁷⁹ Br), 333, 315, 288. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1515, 1375, 1295, 1250, 1175, 1030, 840.

[0373]

Reference Example 4-112 Compound in which R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = H, configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 169-171 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 9.28Hz), 7.14 (1H, ddd, J = 7.
81,1.95,0.98Hz), 7.21 (2H, dm, J = 9.28Hz), 7.25 (1H, dd,
J = 7.81,7.81Hz), 7.33 (1H, dd, J = 1.95,1.95Hz), 7.51 (1
H, ddd, J = 7.81,1.95,0.98Hz). Mass spectrum (m / z): 332 (M ⁺ , ⁷⁹ Br), 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 2400-3600, 1685, 159
5, 1570, 1555, 1505, 142
0, 1275, 1250, 1170, 102
0,825.

[0374]

[Reference Example 4-113] R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = H, arrangement = E
Compound yield (%) = 96. Melting point (recrystallization solvent) = 131-132 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.20 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.7
9Hz), 7.18-7.24 (2H, m), 7.40-7.44 (1H, m), 7.46-7.54
(1H, m). Mass spectrum (m / z): 332 (M ⁺ , ⁷⁹ Br), 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1610, 1560, 1510, 1470, 1420, 1295, 1245, 1
175, 1030, 835.

[0375]

[Reference Example 4-114] Compound with R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 55. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.33Hz), 3.82 (3H, s), 4.04 (2H, q, J = 7.33Hz), 6.32 (1H,
s), 6.85 (2H, dm, J = 8.79Hz), 6.91 (1H, ddd, J = 9.53,2.57,
1.47Hz), 6.99 (1H, dm, J = 7.69Hz), 7.03-7.11 (1H, m), 7.
23 (2H, dm, J = 8.79Hz), 7.35 (1H, ddd, J = 7.69,7.69,5.87H
z). Mass spectrum (m / z): 300 (M ⁺ ), 271, 255, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1585, 1510, 1440, 1370, 1275, 1250, 1160, 1030,
830.

[0376]

[Reference Example 4-115] Compound with R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.27 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 6.98 (1H, ddd, J = 10.25,2.4
4,1.96Hz), 7.05 (1H, dddd, J = 8.30,8.30,2.44,0.98Hz),
7.08-7.12 (1H, m), 7.15 (2H, dm, J = 8.79Hz), 7.29 (1H, ddd,
J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 300 (M ⁺ ), 271, 255, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1585, 1510, 1485, 1440, 1370, 1295, 1280, 1245,
1170, 1030, 1030, 870, 830.

[0377]

[Reference Example 4-116] Compound with R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 166-167 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.91 (1H, ddd, J = 9.
76,2.44,1.46Hz), 6.95-7.01 (1H, m), 7.07 (1H, dddd, J =
8.30,8.30,2.44,0.97Hz), 7.21 (2H, dm, J = 8.79Hz), 7.33
(1H, ddd, J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 272 (M ⁺ ), 255, 227. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600 ,
1695, 1600, 1515, 1440, 1285, 1255, 1180, 1120, 10
35.

[0378]

[Reference Example 4-117] Compound with R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 133-135 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.23 (1H, s), 6.89 (2H, dm, J = 8.79Hz), 6.96 (1H, ddd, J = 9.
77,1.96,1.96Hz), 7.02-7.12 (2H, m), 7.15 (2H, dm, J = 8.7
9Hz), 7.30 (1H, ddd, J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 272 (M ⁺ ), 255, 227. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 2400-3600, 1690, 161
0, 1580, 1510, 1485, 1440,
1290, 1245.

[0379]

[Reference Example 4-118] R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 56. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.08 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.03 (2H, q, J = 7.32Hz), 6.37 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.21 (2H, dm, J = 8.79Hz), 7.
37-7.43 (1H, m), 7.44-7.47 (1H, m), 7.48-7.55 (1H, m),
7.61-7.67 (1H, m). Mass spectrum (m / z): 350 (M ⁺ ), 331, 321, 305, 278. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1510, 1325, 1255, 1165, 1130, 1070, 1030.

[0380]

[Reference Example 4-119] R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement = E
Compound yield (%) = 15. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.18 (3H, t, J =
7.33Hz), 3.85 (3H, s), 4.11 (2H, q, J = 7.33Hz), 6.28 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.79Hz), 7.
37-7.53 (2H, m), 7.56-7.64 (2H, m). Mass spectrum (m / z): 350 (M ⁺ ), 331, 321, 305, 278. Infrared absorption spectrum ν _max (CHCl ₃ ). cm-1: 1710, 161
0, 1510, 1370, 1330, 1295, 1245, 1170, 1150, 1130,
1070, 1030.

[0380]

[Reference Example 4-120] R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, arrangement = Z
Compound yield (%) = 91. Melting point (recrystallization solvent) = 165-167 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.33 (1H, s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.7
9Hz), 7.37 (1H, br.d, J = 7.82Hz), 7.45 (1H, br.s), 7.48 (1
H, br.dd, J = 7.82,7.82Hz), 7.63 (1H, br.d, J = 7.82Hz). Mass spectrum (m / z): 322 (M ⁺ ), 305, 277, 263. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1600, 1575, 1510, 1440, 1325, 1310, 1290, 1
260, 1180, 1150, 1130, 1070.

[0382]

[Reference Example 4-121] R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = Et, configuration = E Compound in yield = 23. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.32Hz), 1.10 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
7 (2H, t, J = 6.84Hz), 4.04 (2H, q, J = 7.32Hz), 6.35 (1H, s),
6.82-6.92 (3H, m), 7.16-7.40 (6H, m).

[0383]

[Reference Example 4-122] Compound with R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = Et, configuration = Z Yield (%) = 47. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.32Hz), 1.12 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.32Hz), 6.34 (1H, s),
6.72-6.96 (3H, m), 7.23-7.38 (6H, m).

[0384]

[Reference Example 4-123] Compound with R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = H, configuration = E Yield (%) = 51. Melting point (recrystallization solvent) = 120-122 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.86 (2H, t, J = 6.70Hz), 6.3
1 (1H, s), 6.78-6.85 (2H, m), 6.88-6.94 (1H, m), 7.16-7.
28 (3H, m), 7.28-7.40 (3H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240,
223. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-360
0, 1690, 1610, 1600, 1580, 1485, 1440, 1400, 1285.

[0385]

[Reference Example 4-124] Compound with R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = H, configuration = Z Yield (%) = 67. Melting point (recrystallization solvent) = 120-122 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.89 (2H, t, J = 6.84Hz), 6.3
1 (1H, s), 6.73 (1H, dd, J = 2.44,1.47Hz), 6.78 (1H, ddd, J =
7.32,1.47,0.98Hz), 6.91 (1H, ddd, J = 8.30,2.44,0.98H
z), 7.22-7.40 (6H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240, 223. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1680, 1590, 1570, 1480, 1440, 1425, 1390, 1275, 11
00.

[0386]

[Reference Example 4-125] Compound in which R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 64. Melting point (recrystallization solvent) = 116-118 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.09 (2H, d, J = 1.83Hz), 7.2
1 (2H, dm, J = 8.79Hz), 7.37 (1H, t, J = 1.83Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 321, 305, 278. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1585, 1560, 1510, 1370, 1345, 1290, 1270, 1250,
1170, 1160, 1030, 860, 830.

[0387]

[Reference Example 4-126] Compound in which R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 19. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.85 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.23 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.79Hz), 7.
16 (2H, d, J = 1.96Hz), 7.35 (1H, t, J = 1.96Hz) .Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 321, 305, 278. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1580, 1560, 1510, 1415, 1370, 1350, 1290, 1245,
1170, 1030, 860, 835.

[0388]

[Reference Example 4-127] Compound with R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 71. Melting point (recrystallization solvent) = 214-216 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.78 (3H, s),
6.37 (1H, s), 6.94 (2H, dm, J = 8.79Hz), 7.17 (2H, d, J = 1.95
Hz), 7.23 (2H, dm, J = 8.79Hz), 7.57 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared Absorption spectrum ν _max (KBr) cm-1: 2400-3400, 1
695, 1670, 1600, 1580, 1560, 1510, 1290, 1260, 121
5, 1185, 1170, 1035, 840, 800.

[0389]

[Reference Example 4-128] Compound with R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 80. Melting point (recrystallization solvent) = 169-171 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.19 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.7
9Hz), 7.14 (2H, d, J = 1.95Hz), 7.36 (1H, t, J = 1.95Hz) .Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared Absorption spectrum ν _max (KBr) cm-
1: 2400-3400, 1700, 1675,
1610, 1580, 1560, 1510, 1
425, 1350, 1280, 1250, 12
20, 1175, 1030, 850, 835,
805.

[0390]

[Reference Example 4-129] Compound in which R ¹ = 2,4-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 83. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.14 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.48 (1H,
s), 6.85 (2H, dm, J = 8.80Hz), 7.09 (1H, d, J = 8.42Hz), 7.2
4 (2H, dm, J = 8.80Hz), 7.30 (1H, dd, J = 8.42,1.84Hz), 7.47
(1H, d, J = 1.84 Hz) .Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1510, 1280, 1255, 1170, 1030, 830.

[0391]

[Reference Example 4-130] Compound with R ¹ = 2,4-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 90. Melting point (recrystallization solvent) = 162-164 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.44 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 7.07 (1H, d, J = 8.30
Hz), 7.22 (2H, dm, J = 8.79Hz), 7.28 (1H, dd, J = 8.30,1.95H
z), 7.45 (1H, d, J = 1.95Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1700, 160
0, 1590, 1510, 1285, 1260, 1180, 1155, 830.

[0390]

[Reference Example 4-131] Compound with R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 60. Melting point (recrystallization solvent) = 119-121 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.06 (2H, q, J = 7.33Hz), 6.56 (1H,
s), 6.87 (2H, dm, J = 9.28Hz), 7.22-7.34 (1H, m), 7.30 (2
H, dm, J = 9.27Hz), 7.35-7.41 (2H, m). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1575, 1510, 1430, 1290, 1275, 1255, 1160, 1025,
830.

[0393]

[Reference Example 4-132] Compound in which R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 222-224 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.53 (1H, s), 6.87 (2H, dm, J = 8.79Hz), 7.20-7.40 (3H, m),
7.28 (2H, dm, J = 8.79Hz) .Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 307, 305, 287,
272. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1700, 1600, 1575, 1515, 1430, 1290, 1260, 1180, 11
60, 835.

[0394]

[Reference Example 4-133] Compound in which R ¹ = 2,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 82. Melting point (recrystallization solvent) = 98-100 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.47 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.15 (1H, d, J = 2.44Hz), 7.2
5 (2H, dm, J = 8.79Hz), 7.29 (1H, dd, J = 8.30,2.44Hz), 7.37
. (1H, d, J = 8.30Hz) Mass spectrum (m / z): 350 ( M +, 35 Cl), 315, 305, 287. Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1: 1715, 160
5, 1515, 1470, 1295, 1280, 1260, 1170, 1165, 1100,
1030, 835.

[0395]

[Reference Example 4-134] Compound with R ¹ = 2,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 201-203 ° C (tetrahydrofuran
-hexane) NMR spectrum (270 MHz, d ₆ -DMSO) δ ppm: 3.77 (3H,
s), 6.53 (1H, s), 6.94 (2H, dm, J = 8.79Hz), 7.25 (2H, dm, J
= 8.79Hz), 7.29 (1H, d, J = 2.44Hz), 7.46 (1H, dd, J = 8.79,
2.44Hz), 7.53 (1H, d, J = 8.79Hz), 12.13 (1H, br.s). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 287, 272. Infrared Absorption spectrum ν _max (KBr) cm-1: 2200-3300, 1
690, 1595, 1580, 1510, 1465, 1425, 1345, 1280, 126
0, 1210, 1185, 1160, 1030, 835.

[0396]

[Reference Example 4-135] Compound with R ¹ = 2,3-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 70. Melting point (recrystallization solvent) = 88-90 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.81 (3H, s), 4.03 (2H, q, J = 7.32Hz), 6.47 (1H,
s), 7.07 (1H, dd, J = 7.70,1.47Hz), 7.20-7.40 (3H, m), 7.
49 (1H, dd, J = 8.06,1.47Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1 : 1710, 160
0, 1575, 1510, 1455, 1410, 1370, 1350, 1280, 1255,
1160, 1030, 830.

[0397]

[Reference Example 4-136] Compound in which R ¹ = 2,3-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, and configuration = Z Yield (%) = 89. Melting point (recrystallization solvent) = 129-131 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.44 (1H, s), 6.85 (2H, dm, J = 8.78Hz), 7.05 (1H, dd, J = 7.8
1,1.47Hz), 7.23 (1H, dd, J = 7.81,7.81Hz), 7.24 (2H, dm, J
= 8.78Hz), 7.47 (1H, dd, J = 7.81,1.47Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl),
287.

[0398]

[Reference Example 4-137] Compound in which R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 57. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.11 (3H, t, J =
7.32Hz), 2.31 (6H, s), 3.81 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.26 (1H, s), 6.80 (2H, br.s), 6.83 (2H, dm, J = 9.16H
z), 6.99 (1H, t, J = 0.73Hz), 7.25 (2H, dm, J = 9.16Hz). Mass spectrum (m / z): 310 (M ⁺ ), 281, 265, 238. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1460, 1440, 1370, 1350, 1290, 1245, 1170,
1030, 850,840.

[0399]

[Reference Example 4-138] Compound of R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 24. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.32Hz), 2.27 (3H, s), 2.28 (3H, s), 3.84 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.24 (1H, s), 6.895 (2H, dm, J = 8.79H
z), 6.904 (2H, br.s), 6.99 (1H, br.s), 7.15 (2H, dm, J = 8.
79Hz). Mass spectrum (m / z): 310 (M ⁺ ), 281, 265, 238. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1460, 1440, 1370, 1350, 1290, 1245, 1170,
1030, 850,840.

[0400]

[Reference Example 4-139] Compound in which R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 156-158 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.31 (6H, s),
3.81 (3H, s), 6.24 (1H, s), 6.82 (2H, br.s), 6.84 (2H, dm,
J = 8.78Hz), 7.01 (1H, br.s), 7.22 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 282 (M ⁺ ), 267, 237. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1600, 1570, 1510, 1285, 1250, 1175, 1030, 83
Five.

[0401]

[Reference Example 4-140] Compound with R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 165-166 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.28 (6H, s),
3.85 (3H, s), 6.20 (1H, s), 6.86-6.90 (2H, m), 6.88 (2H, d
m, J = 8.79Hz), 7.01 (1H, br.s), 7.16 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 282 (M ⁺ ), 267, 237. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 2200-3700,
1690, 1610, 1510, 1290, 1240, 1175, 1030, 835.

[0402]

Reference Example 4-141 Compound with R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = Et, Configuration = E Yield (%) = 13. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.33Hz), 1.28 (3H, t, J = 7.69Hz), 2.70 (2H, q, J = 7.69Hz),
4.07 (2H, q, J = 7.33Hz), 6.29 (1H, s), 7.11 (2H, dm, J = 8.4
3Hz), 7.17 (1H, ddd, J = 7.69,2.20,1.47Hz), 7.21 (2H, dm,
J = 8.43Hz), 7.25 (1H, dd, J = 7.69,7.69Hz), 7.29 (1H, dd, J
= 1.47,1.47Hz), 7.32 (1H, ddd, J = 7.69,2.20,1.47Hz). Mass spectrum (m / z): 314 (M ⁺ , ³⁵ Cl), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 1710, 1610, 1570, 147
5, 1370, 1350, 1260, 117
0, 1030, 875, 840.

[0403]

[Reference Example 4-142] Compound with R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = Et, configuration = Z Yield (%) = 41. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.69Hz), 2.66 (2H, q, J = 7.69Hz),
6.36 (1H, s), 7.10 (1H, ddd, J = 6.96,1.83,1.83Hz), 7.16
(2H, dm, J = 8.43Hz), 7.18-7.21 (1H, m), 7.21 (2H, dm, J = 8.
43Hz), 7.27-7.34 (1H, m), 7.35 (1H, ddd, J = 8.06,1.83,1.
Mass spectrum (m / z): 314 (M ⁺ , ³⁵ Cl), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1610, 1595, 1565, 1370, 1350, 1270, 1170, 1030,
880, 835.

[0404]

[Reference Example 4-143] Compound with R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 99-100 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.28 (3H, t, J =
7.32Hz), 2.70 (2H, q, J = 7.32Hz), 6.26 (1H, s), 7.11 (2H,
dm, J = 8.30Hz), 7.15 (1H, ddd, J = 7.81,1.46,1.46Hz), 7.2
0 (2H, dm, J = 8.30Hz), 7.26 (1H, dd, J = 7.81,7.81Hz), 7.34
(1H, ddd, J = 7.81,1.46,0.98Hz) .Mass spectrum (m / z): 286 (M ⁺ , ³⁵ Cl), 271,257,241.Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1690, 161
0, 1570, 1420, 1270, 1180, 840.

[0405]

[Reference Example 4-144] Compound with R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 146-148 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.23 (3H, t, J =
7.82Hz), 2.66 (2H, q, J = 7.82Hz), 6.34 (1H, s), 7.10 (1H,
ddd, J = 6.84,1.47,1.47Hz), 7.13-7.22 (5H, m), 7.27-7.3
4 (1H, m), 7.35 (1H, ddd, J = 8.30,1.47,1.47Hz). Mass spectrum (m / z): 286 (M ⁺ , ³⁵ Cl), 271, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1690, 161
0, 1570, 1420, 1270, 1180, 840.

[0406]

[Reference Example 4-145] Compound with R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 62. Melting point (recrystallization solvent) = 104-105 ° C. (Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.08 (3H, t, J =
7.33Hz), 3.83 (3H, s), 4.02 (2H, q, J = 7.33Hz), 6.42 (1H,
s), 6.88 (2H, dm, J = 8.80Hz), 7.18 (2H, dm, J = 8.80Hz), 7.
64-7.69 (2H, m), 7.88-7.92 (1H, m). Mass spectrum (m / z): 418 (M ⁺ ), 399, 390, 373, 346. Infrared absorption spectrum ν _max (CHCl ₃ ). cm-1: 1710, 160
0, 1510, 1460, 1390, 1330, 1280, 1175, 1140.

[0407]

[Reference Example 4-146] Compound with R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.19 (3H, t, J =
7.33Hz), 3.86 (3H, s), 4.12 (2H, q, J = 7.33Hz), 6.31 (1H,
s), 6.93 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
71-7.75 (2H, m), 7.85-7.89 (1H, m). Mass spectrum (m / z): 418 (M ⁺ ), 399, 389, 373, 346. Infrared absorption spectrum ν _max (CHCl ₃ ). cm
-1: 1720, 1610, 1515, 146
0, 1370, 1350, 1280, 124
5, 1175, 1140.

[0408]

[Reference Example 4-147] Compound with R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 92. Melting point (recrystallization solvent) = 197-199 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
6.40 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.7
9Hz), 7.62-7.67 (2H, m), 7.87-7.92 (1H, m). Mass spectrum (m / z): 390 (M ⁺ ), 373, 345. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 3700-2200,
1690, 1600, 1510, 1460, 1420, 1390, 1330, 1280, 1
180, 1140.

[0409]

[Reference Example 4-148] Compound of R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 144-146 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.87 (3H, s),
6.27 (1H, s), 6.93 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.7
9Hz), 7.69-7.74 (2H, m), 7.87-7.91 (1H, m). Mass spectrum (m / z): 390 (M ⁺ ), 373, 345. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 3200-2400,
1700, 1610, 1515, 1460, 1380, 1350, 1280, 1250, 1
180, 1140.

[0410]

[Reference Example 4-149] Compound with R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = Et, configuration = Z Yield (%) = 41. Melting point (recrystallization solvent) = 104-106 ° C. (Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 1.42 (3H, t, J = 6.96Hz), 4.05 (2H, q, J = 6.96Hz),
4.06 (2H, q, J = 7.33Hz), 6.32 (1H, s), 6.85 (2H, dm, J = 8.7
9Hz), 7.09 (2H, d, J = 1.83Hz), 7.20 (2H, dm, J = 8.79Hz),
7.37 (1H, t, J = 1.83Hz) .Mass spectrum (m / z): 364 (M ⁺ , ³⁵ Cl), 319, 292. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 160
5, 1590, 1565, 1515, 1370, 1350, 1275, 1255, 1160,
1040.

[0411]

[Reference Example 4-150] Compound with R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = Et, configuration = E Yield (%) = 12. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 1.44 (3H, t, J = 7.33Hz), 4.07 (2H, q, J = 7.33Hz),
4.09 (2H, q, J = 7.32Hz), 6.22 (1H, s), 6.90 (2H, dm, J = 8.7
9Hz), 7.11 (2H, dm, J = 8.79Hz), 7.16 (2H, d, J = 1.95Hz),
. 7.34 (1H, t, J = 1.95Hz) Mass spectrum (m / z): 364 ( M +, 35 Cl), 319, 292. Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1: 1715, 161
0, 1590, 1560, 1515, 1395, 1370, 1350, 1290, 1245,
1175.

[0412]

[Reference Example 4-151] Compound with R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = H, configuration = Z Yield (%) = 86. Melting point (recrystallization solvent) = 220-222 ° C. (MeOH-Et ₂ O) NMR spectrum (270 MHz, DMSO-d ₆ ) δ ppm: 1.32 (3H, t,
J = 6.84Hz), 4.04 (2H, q, J = 6.84Hz), 6.37 (1H, s), 6.92 (2
H, dm, J = 8.79Hz), 7.18 (2H, d, J = 1.95Hz), 7.21 (2H, dm, J =
8.79Hz), 7.60 (1H, t, J = 1.95Hz), 12.18 (1H, br.s). Mass spectrum (m / z): 336 (M ⁺ , ³⁵ Cl), 308, 291. Infrared absorption spectrum ν _max (KBr) cm-1: 3400-2200, 1
695, 1670, 1625, 1600, 1585, 1560, 1515, 1440, 129
0, 1260, 1215, 1185, 1165, 840.

[0413]

[Reference Example 4-152] Compound of R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = H, configuration = E Yield (%) = 89. Melting point (recrystallization solvent) = 174-176 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.83Hz), 4.08 (2H, q, J = 6.83Hz), 6.19 (1H, s), 6.89 (2H,
dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.79Hz), 7.15 (2H, d, J = 1.
95Hz), 7.36 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 336 (M ⁺ , ³⁵ Cl), 308, 291. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2200,
1690, 1610, 1585, 1560, 1510, 1420, 1390, 1290, 1
245, 1175.

[0414]

[Reference Example 4-153] R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 44. Melting point (recrystallization solvent) = 73-75 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.32Hz), 2.66 (2H, q, J = 7.32Hz),
4.07 (2H, q, J = 7.32Hz), 6.38 (1H, s), 7.10 (2H, d, J = 1.95
Hz), 7.13-7.23 (4H, m), 7.37 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 348 (M ⁺ , ³⁵ Cl), 319, 303, 276. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1605, 1585, 1560, 1410, 1370, 1345, 1270, 1160.

[0415]

[Reference Example 4-154] R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 13. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.13 (3H, t, J =
7.32Hz), 1.28 (3H, t, J = 7.32Hz), 2.70 (2H, q, J = 7.32Hz),
4.07 (2H, q, J = 7.32Hz), 6.27 (1H, s), 7.09 (2H, dm, J = 8.3
0Hz), 7.17 (2H, d, J = 1.95Hz), 7.22 (2H, dm, J = 8.30Hz),
. 7.34 (1H, t, J = 1.95Hz) Mass spectrum ^{(m / z): 348 (} M +, 35 Cl),
319, 303, 276. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 16
10, 1585, 1560, 1410, 1370, 1350, 1260, 1170.

[0416]

[Reference Example 4-155] R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 90. Melting point (recrystallization solvent) = 206-208 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, DMSO-d ₆ ) δ ppm: 1.17 (3H, t,
J = 7.32Hz), 2.61 (2H, q, J = 7.32Hz), 6.43 (1H, s), 7.16-
7.28 (4H, m), 7.20 (2H, d, J = 1.95Hz), 7.61 (1H, t, J = 1.95H
z), 12.32 (1H, br.s). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 291, 275. Infrared absorption spectrum ν _max (KBr) cm-1: 3400-2200, 1
695, 1670, 1620, 1605, 1580, 1560, 1415, 1275, 122
0, 835, 805.

[0417]

[Reference Example 4-156] R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 99. Melting point (recrystallization solvent) = 162-164 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.28 (3H, t, J =
7.32Hz), 2.70 (2H, q, J = 7.32Hz), 6.23 (1H, s), 7.09 (2H,
dm, J = 8.30Hz), 7.14 (2H, d, J = 1.95Hz), 7.21 (2H, dm, J = 8.
30Hz), 7.36 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 291, 275. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1610, 1595, 1560, 1415, 1265, 1180, 860, 83
Five.

[0418]

[Reference Example 4-157] R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 48. Melting point (recrystallization solvent) = 65-66 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.07 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.69-6.89 (3H, m), 6.86 (2H, dm, J = 9.16Hz), 7.22 (2
H, dm, J = 9.16Hz). Mass spectrum (m / z): 318 (M ⁺ ), 289, 273, 246. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 160
5, 1515, 1435, 1375, 1290, 1255, 1170, 1120.

[0419]

[Reference Example 4-158] R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 20. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.85 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.26 (1H,
s), 6.75-6.88 (3H, m), 6.91 (2H, dm, J = 8.79Hz), 7.13 (2
H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ ), 289, 273, 246. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 162
0, 1610, 1595, 1515, 1435, 1370, 1295, 1250, 1170,
1120.

[0420]

[Reference Example 4-159] R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 87. Melting point (recrystallization solvent) = 170-172 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.30 (1H, s), 6.67-6.90 (3H, m), 6.86 (2H, dm, J = 9.28Hz),
7.21 (2H, dm, J = 9.28Hz). Mass spectrum (m / z): 290 (M ⁺ ), 273, 245. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
−1: 3600-2400, 1695, 162
5, 1600, 1515, 1430, 1290,
1260, 1180, 1120.

[0421]

[Reference Example 4-160] Compound with R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 90. Melting point (recrystallization solvent) = 140-142 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.22 (1H, s), 6.75-6.94 (3H, m), 6.90 (2H, dm, J = 8.79Hz),
7.14 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 290 (M ⁺ ), 273, 245. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1695, 1625, 1610, 1595, 1515, 1435, 1295, 1250, 1
175, 1125.

[0422]

[Reference Example 4-161] Compound in which R ¹ = 3-CNPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 43. Melting point (recrystallization solvent) = 105-106 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.83 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.38 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.79Hz), 7.
45 (1H, ddd, J = 7.69,1.47,1.47Hz), 7.48-7.52 (1H, m), 7.
51 (1H, ddd, J = 7.69,7.69,0.73Hz), 7.68 (1H, ddd, J = 7.69,
1.47,1.47Hz). Mass spectrum (m / z): 307 (M ⁺ ), 278, 262, 235. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2240, 171
5, 1610, 1515, 1375, 1280, 1260, 1170, 1030, 835.

[0423]

Reference Example 4-162 Compound with R ¹ = 3-CNPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 8. Melting point (recrystallization solvent) = 193-194 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
6.34 (1H, s), 6.86 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.7
9Hz), 7.44 (1H, ddd, J = 7.82,1.47,1.47Hz), 7.45-7.50 (1
H, m), 7.48 (1H, dd, J = 7.82,7.82Hz), 7.67 (1H, ddd, J = 7.8
2,1.47,1.47Hz) .Mass spectrum (m / z): 279 (M ⁺ ), 262,
234. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
2240, 1690, 1600, 1570, 1510, 1425, 1285, 1260, 1
180, 1035, 835.

[0424]

[Reference Example 4-163] Compound with R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = Et, configuration = Z Yield (%) = 16. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.33Hz), 1.41 (3H, t, J = 6.96Hz), 4.038 (2H, q, J = 6.96H
z), 4.042 (2H, q, J = 7.33Hz), 6.32 (1H, s), 6.83 (2H, dm, J
= 8.79Hz), 6.91 (1H, ddd, J = 9.53,2.56,1.46Hz), 6.95-7.
02 (1H, m), 7.07 (1H, dddd, J = 8.43,8.43,2.56,1.10Hz),
7.22 (2H, dm, J = 8.79Hz), 7.34 (1H, ddd, J = 8.43,8.43,5.86
Mass spectrum (m / z): 314 (M ⁺ ), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1580, 1510, 1475, 1370, 1270, 1250, 1160, 1115,
1035.

[0425]

[Reference Example 4-164] Compound with R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = Et, configuration = E Yield (%) = 8. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.32Hz), 1.43 (3H, t, J = 6.83Hz), 4.07 (2H, q, J = 6.83Hz),
4.09 (2H, q, J = 7.32Hz), 6.26 (1H, s), 6.89 (2H, dm, J = 8.7
9Hz), 6.94-7.13 (3H, m), 7.13 (2H, dm, J = 8.79Hz), 7.28
(1H, ddd, J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 314 (M ⁺ ), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1605, 1580, 151
0, 1485, 1475, 1440, 137
0, 1240, 1170, 1130, 103
5.

[0426]

[Reference Example 4-165] R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = H, arrangement = Z
Compound yield (%) = 91. Melting point (recrystallization solvent) = 154-155 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.41 (3H, t, J =
6.83Hz), 4.04 (2H, q, J = 6.83Hz), 6.28 (1H, s), 6.83 (2H,
dm, J = 8.79Hz), 6.90 (1H, ddd, J = 9.28,2.44,1.46Hz), 6.9
4-7.00 (1H, m), 7.06 (1H, dddd, J = 8.30,8.30,2.44,0.98H
z), 7.20 (2H, dm, J = 8.79Hz), 7.33 (1H, ddd, J = 8.30,8.30,
5.86Hz). Mass spectrum (m / z): 286 (M ⁺ ), 269, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1595, 1510, 1435, 1285, 1250, 1175, 1115, 10
35.

[0427]

[Reference Example 4-166] Compound in which R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 148-149 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.83Hz), 4.07 (2H, q, J = 6.83Hz), 6.22 (1H, s), 6.88 (2H,
dm, J = 8.79Hz), 6.92-7.00 (1H, m), 7.01-7.12 (2H, m), 7.
14 (2H, dm, J = 8.79Hz), 7.29 (1H, ddd, J = 8.30,8.30,5.86H
z). Mass spectrum (m / z): 286 (M ⁺ ), 269, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1605, 1580, 1510, 1485, 1440, 1285, 1265, 1
240, 1170, 1035.

[0428]

[Reference Example 4-167] Compound in which R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 49. Melting point (recrystallization solvent) = 83-85 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.33Hz), 2.33 (3H, s), 3.82 (3H, s), 4.05 (2H, q, J = 7.33H
z), 6.29 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.86-6.90 (1
H, m), 6.98-7.03 (1H, m), 7.14-7.20 (1H, m), 7.23 (2H, d
Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 301, 285, 258. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1575, 1510, 1290, 1275, 1250, 1165, 1030, 830.

[0429]

[Reference Example 4-168] Compound with R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 17. Melting point (recrystallization solvent) = oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.33Hz), 2.30 (3H, s), 3.85 (3H, s), 4.09 (2H, q, J = 7.33H
z), 6.23 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 6.95-7.02 (1
H, m), 7.04-7.09 (1H, m), 7.13-7.19 (1H, m), 7.14 (2H, d
m, J = 8.79Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 301, 285, 258. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1570, 1510, 1290, 1280, 1245, 1170, 1140, 1030.

[0430]

[Reference Example 4-169] Compound in which R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 93. Melting point (recrystallization solvent) = 190-192 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
3.82 (3H, s), 6.26 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.85
-6.90 (1H, m), 6.96-7.01 (1H, m), 7.14-7.20 (1H, m), 7.2
1 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 302 (M ⁺ , ³⁵ Cl), 285, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 3600-2400, 1690, 160
0, 1570, 1510, 1280, 1250,
1175, 1030, 830.

[0431]

[Reference Example 4-170] R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H,
Configuration = Compound of E Yield (%) = 91. Melting point (recrystallization solvent) = 156-158 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.30 (3H, s),
3.85 (3H, s), 6.18 (1H, s), 6.89 (2H, dm, J = 8.79Hz), 6.94
-6.99 (1H, m), 7.00-7.06 (1H, m), 7.14-7.20 (1H, m), 7.1
4 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 302 (M ⁺ , ³⁵ Cl), 285, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400 ,
1690, 1605, 1570, 1510, 1290, 1245, 1170, 1030, 8
70, 850, 830.

[0432]

[Reference Example 4-171] Compound in which R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = Et, configuration = Z Yield (%) = 17. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.12 (3H, t, J =
7.32Hz), 1.41 (3H, t, J = 6.96Hz), 2.33 (3H, s), 4.04 (2H,
q, J = 6.96Hz), 4.05 (2H, q, J = 7.32Hz), 6.29 (1H, s), 6.83
(2H, dm, J = 8.79Hz), 6.85-6.91 (1H, m), 6.98-7.02 (1H,
m), 7.15-7.19 (1H, m), 7.21 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 315, 299, 272. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1570, 1510, 1475, 1365, 1270, 1250, 1160, 1035,
850, 830.

[0433]

[Reference Example 4-172] R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = Et, configuration = E Compound yield (%) = 6. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.16 (3H, t, J =
7.32Hz), 1.43 (3H, t, J = 6.84Hz), 2.30 (3H, s), 4.07 (2H,
q, J = 6.84Hz), 4.08 (2H, q, J = 7.32Hz), 6.22 (1H, s), 6.89
(2H, dm, J = 8.79Hz), 6.95-7.01 (1H, m), 7.04-7.09 (1H,
m), 7.12-7.18 (1H, m), 7.12 (2H, dm, J = 8.79Hz) .Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 315, 299, 272. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
5, 1570, 1510, 1475, 1365, 1280, 1240, 1165, 1140,
1110, 1035, 850.

[0434]

[Reference Example 4-173] Compound in which R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = H, configuration = Z Yield (%) = 89. Melting point (recrystallization solvent) = 197-199 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.41 (3H, t, J =
6.84Hz), 2.32 (3H, s), 4.04 (2H, q, J = 6.84Hz), 6.26 (1H,
s), 6.83 (2H, dm, J = 9.28Hz), 6.85-6.91 (1H, m), 6.96-7.
02 (1H, m), 7.14-7.20 (1H, m), 7.20 (2H, dm, J = 9.28Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271.

[0435]

[Reference Example 4-174] Compound with R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = H, configuration = E Yield (%) = 86. Melting point (recrystallization solvent) = 163-165 ° C. (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.84Hz), 2.30 (3H, s), 4.07 (2H, q, J = 6.84Hz), 6.17 (1H,
s), 6.87 (2H, dm, J = 8.79Hz), 6.93-7.00 (1H, m), 7.00-7.
07 (1H, m), 7.14-7.20 (1H, m), 7.13 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271.

[0436]

Reference Example 5 Methyl (E) -3,5-diphenylpent-2-en-4 -inate Methyl Z-3-bromocinnamate (1.000 g) and bis (triphenylphosphine) dichloropalladium (0.029 g) Cuprous iodide (0.158 g) and phenylacetylene (0.424 g) were added to a diethylamine (25 ml) solution of and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off, water was added to the residue, and the mixture was extracted twice with benzene.
It was subjected to column chromatography using (70-230 mesh, 25 g). Fractions eluted with hexane-ethyl acetate (39: 1) were collected to give the title compound (1.043g). Melting point: 73-75 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.84 (3H,
s); 6.60 (1H, s); 7.34-7.82 (10H, m). Mass spectrum (m / z): 262 (M ⁺ ); 247; 231. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2200, 171
0, 1600, 1590, 1575, 1490, 1450, 1435, 1365, 1275,
1165.

[0437]

Reference Example 6 (E) -3,5-diphenylpent-2-ene-4-ynoic acid Compound of Reference Example 5 (1.000 g), methanol (15 ml), tetrahydrofuran (7.5 ml) and 10% hydroxylated A mixture of aqueous sodium solution (15 ml) was stirred at room temperature for 18 hours. After distilling off the solvent, the residue was diluted with water and extracted twice with ether. The extract is washed with water, dried, and concentrated to give the indicated compound.
(0.912 g) was obtained. Melting point: 124-126 ° C. (methylene chloride-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 6.65 (1H,
s); 7.30-7.90 (10H, m). Mass spectrum (m / z): 248 (M ⁺ ); 231; 220. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2400-3600
(broad), 2200, 1685, 1600, 1590, 1575, 1490, 1450,
1280, 1180.

[0438]

[Reference Example 7] 3,3-bis (4-methoxyphenyl) -3-hydroxy-2-methyi
Ethyl lepropionate Ethyl 2-bromopropionate (8.25 g), 4,4'-dimethoxybenzophenone (11.81 g), zinc (7.16 g) and benzene (70 ml) were heated to reflux on an oil bath for 4 hours. .. After allowing to cool, the reaction solution was filtered, and the filtrate was washed with 10% sulfuric acid, water and saturated saline. After drying, the solvent was distilled off, and the residue was subjected to flash column chromatography using silica gel (-400 mesh, 300 g). Hexane-ethyl acetate (10
The title compound (7.92 g) was obtained as white crystals from the fraction eluted at 0: 2). Melting point: 67-69 ° C (methylene chloride-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (6H,
t, J = 6.84Hz); 3.54 (1H, q, J = 6.84Hz); 3.75 (6H, s); 3.95
-4.15 (2H, m); 4.61 (1H, s); 6.80 (4H, dm, J = 8.79Hz); 7.3
3 (2H, dm, J = 8.79Hz), 7.44 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 344 (M ⁺ ); 326; 299; 281; 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1710, 161
0, 1510, 1460, 1375, 1340, 1245, 1170. Elemental analysis value (as C ₂₀ H ₂₄ O ₅ ) Calculated value: C; 69.75, H; 7.02. Measured value: C; 69.89, H; 7.10.

[0439]

[Reference Example 8] 3,3-bis (4-methoxyphenyl) -2-methylacrylic acid
Ethyl phosphorus oxychloride (4.10 ml) was added dropwise to a solution of the compound of Reference Example 7 (7.02 g) in benzene (140 ml) at 5-10 ° C under ice cooling. After stirring at room temperature for 3 hours, the reaction solution was poured into water and extracted 3 times with ether. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried and concentrated.
The residue (6.72 g) was subjected to flash column chromatography using silica gel (100 g). The title compound (6.04 g) from the fraction eluted with hexane-ethyl acetate (95: 5)
Was obtained as an oil. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 0.95 (3H,
t, J = 7.32Hz); 2.05 (3H, s); 3.78 (3H, s); 3.81 (3H, s);
3.97 (2H, q, J = 7.32Hz); 6.79 (2H, dm, J = 8.30Hz); 6.85 (2
H, dm, J = 8.30Hz); 7.03 (2H, dm, J = 8.30Hz); 7.08 (2H, dm, J
= 8.30Hz). Mass spectrum (m / z): 326 (M ⁺ ); 297; 281; 279; 252. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1700, 161
0, 1510, 1465, 1315, 1300, 1280, 1240, 1175, 1125. Elemental analysis value (as C ₂₀ H ₂₂ O ₄ ) Calculated value: C; 73.60, H; 6.79. Measured value: C; 73.39, H; 6.82.

[0440]

Reference Example 9 3,3-bis (4-methoxyphenyl) -2-methylacrylic acid The compound of Reference Example 8 (6.019 g), ethanol (120 ml) and
A mixture of 10% aqueous sodium hydroxide solution (80 ml) at room temperature.
It was stirred for 14 hours. After heating in an oil bath at 100 ° C for 4 hours,
The ethanol was distilled off. The residue was diluted with ice water and washed with ethyl acetate. Concentrated hydrochloric acid was added dropwise to the aqueous layer under ice cooling to adjust the pH to 2, and the mixture was extracted twice with methylene chloride. Wash the extract with water
After drying and concentration, the title compound (5.117 g) was obtained as white crystals. Melting point: 134-135 ° C (methylene chloride-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.06 (3H,
s); 3.80 (3H, s); 3.81 (3H, s); 6.79 (2H, dm, J = 8.79Hz);
6.86 (2H, dm, J = 8.79Hz); 7.06 (2H, dm, J = 8.79Hz); 7.07 (2
H, dm, J = 8.79Hz). Mass spectrum (m / z): 298 (M ⁺ ); 281; 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2400-3600
(broad), 1680, 1610, 1510, 1245, 1175. Elemental analysis (C ₁₈ H ₁₈ as O ₄₎ Calculated: C; 72.47, H; 6.08 Found:. C; 72.11, H; 6. 15.

[0441]

Reference Example 10 N- (3,4,5-trimethoxybenzenesulfoni
) Piperazine N-formylpiperazine (3.80 g) and triethyleneamine
(7.73 ml) and methylene chloride (150 ml) in ice-cooled 3,4,5-trimethoxybenzenesulfonyl chloride.
A solution of (7.40 g) in methylene chloride (75 ml) was added dropwise.
After stirring for 30 minutes at 0-5 ° C, the reaction mixture was poured into water and extracted twice with methylene chloride. The extract was washed with 10% hydrochloric acid and brine, dried and concentrated. The residue (9.86 g) was dissolved in a mixture of tetrahydrofuran (150 ml), methanol (75 ml) and 10% aqueous sodium hydroxide solution (50 ml), and the mixture was stirred at room temperature for 14 hr. The reaction solution was poured into water and extracted 4 times with methylene chloride. Wash the extract with water, dry and concentrate,
The residue was recrystallized from hexane-ethyl acetate to give the title compound (7.02 g). Mp: 131-133 ° C. NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.10
(8H, m); 3.91 (9H, s); 6.96 (2H, s). Mass spectrum (m / z): 316 (M ⁺ ); 232; 85. Elemental analysis value (C ₁₃ H ₂₀ N ₂ O ₅ Calculated: C; 49.35, H; 6.37, N; 8.85, S; 10.13. Found: C; 49.62, H; 6.30, N; 8.55, S; 10.11.

[0442]

[Reference Example 11] 3,3-bis (3-chlorophenyl) acrylic acid 3,3'-dichlorobenzophenone (10.85 g) was used and the same reaction as in Reference Example 1 was carried out to obtain a crude product from methylene chloride-hexane. When recrystallized, the indicated compound (12.32
g) was obtained. Melting point: 114-115 ° C

[0443]

[Reference Example 12] 1- [3,3-bis (3-chlorophenyl) acryloyl] pipet
Compound of Radin Reference Example 11 (5.00 g) and triethylamine (4.75
ml) in methylene chloride (100 ml), diphenylphosphoryl azide (5.51 ml) and N-formylpiperazine (1.9 ml).
3 ml) were added sequentially. The reaction mixture was stirred at room temperature for 18 hours, washed with saturated aqueous sodium hydrogen carbonate solution and water, dried and concentrated. The residue was dissolved in a mixture of ethanol (100 ml) and tetrahydrofuran (50 ml), 10% aqueous sodium hydroxide solution (50 ml) was added, and the mixture was stirred at room temperature for 8 hr.
The reaction solution was poured into water and extracted twice with methylene chloride. The extracts were combined, washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (150 g). Fractions eluting with methylene chloride-methanol (49: 1-9: 1) were collected to give the title compound (5.23 g) as a viscous oil. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.21 (1H,
s); 2.00-2.95 (4H, m); 3.00-3.85 (4H, m); 6.38 (1H, s);
6.90-7.50 (8H, m). Mass spectrum (m / e): 360 (M ⁺ , ³⁵ Cl); 325; 292; 275.

[0444]

[Reference Example 13] (Z)-and (E) -3-phenyl-3- (2-naphthyl) acrylic acid
Using Chill 2-naphthyl phenyl ketone (10.10 g), Reference Example 1
The same reaction as in the first half was performed. The crude product was treated with silica gel (2
Column chromatography using 00 g) and Lobar-
Subjected to medium pressure liquid chromatography using a C column. Fractions eluted with hexane-ethyl acetate were collected,
The E-isomer (2.48 g) was obtained. Melting point: 91-92 ° C (hexane) Elution was continued with the same solvent to obtain an E-isomer (4.44 g). Melting point: 84-85 ° C (hexane)

[0445]

Reference Example 14 (Z) -3-Phenyl-3- (2-naphthyl) acrylic acid The Z-isomer of Reference Example 13 (2.411 g) was added to ethanol (48 ml).
Dissolve it in a mixture of methanol and tetrahydrofuran (24 ml) and
Aqueous sodium hydroxide solution (24 ml) was added, and the mixture was stirred at room temperature for 15 hours. Pour the reaction mixture into water and add concentrated hydrochloric acid to adjust the pH to 2
And extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was recrystallized from methylene chloride-hexane to obtain the target compound (2.005 g). Melting point: 170-172 ° C NMR spectrum (270 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 6.
44 (1H, s); 7.28-7.42 (6H, m); 7.44-7.54 (2H, m); 7.71 (1
H, d, J = 0.73Hz); 7.76-7.91 (3H, m). Mass spectrum (m / e): 274 (M ⁺ ); 257; 229. Elemental analysis value (as C ₁₉ H ₁₄ O ₂ ). Values: C; 83.19, H; 5.14. Found: C; 83.39, H; 5.35.

[0446]

Reference Example 15 ( E) -3-Phenyl-3- (2-naphthyl) acrylic acid The E-isomer (2.219 g) of Reference Example 13 was hydrolyzed in the same manner as in Reference Example 14 to obtain the target compound ( 1.685 g) was obtained. Melting point: 229-231 ° C (ether-tetrahydrofuran) NMR spectrum (270 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 6.
50 (1H, s); 7.23-7.32 (2H, m); 7.36-7.43 (3H, m); 7.43-
7.54 (3H, m); 7.67 (1H, d, J = 1.83Hz); 7.70-7.88 (3H, m). Mass spectrum (m / e): 274 (M ⁺ ); 257; 229. Elemental analysis value ( C ₁₉ H ₁₄ O ₂ ) Calculated: C; 83.19, H; 5.14. Found: C; 83.45, H; 5.33.

[0447]

Reference Example 16 Ethyl (E) -p -isobutyloxycinnamate (E) -p-Hydroxycinnamate (9.61 g) and isobutyl bromide (8.22 g) were dissolved in dimethyl sulfoxide (100 ml), and potassium carbonate ( 13.8 g) and sodium iodide (7.50 g)
Was added and the mixture was heated with stirring at 60 ° C. for 20 hours. After cooling, the reaction solution was poured into 1 liter of water and extracted twice with ethyl acetate. The extract was washed with water, dried and concentrated, and the residue was washed with silica gel (3
Chromatography with 00 g). Fractions eluted with hexane-ethyl acetate (5: 1) were collected to give the target compound as a colorless oil (10.71 g, solidified at low temperature). NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (6H, d, J =
7Hz); 1.28 (3H, t, J = 7Hz); 1.60-2.50 (1H, m); 3.70 (2H,
d, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.26 (1H, d, J = 16Hz); 6.8
6 (2H, dm, J = 9Hz); 7.45 (2H, dm, J = 9Hz); 7.66 (1H, d, J = 16H
z).

[0448]

Reference Example 17 The same reaction as in Reference Example 16 was carried out using ethyl (E) -p -propoxycinnamate (E) -p-hydroxycinnamate (9.61 g) and propyliodide (10.20 g). .. However, sodium iodide was not used. Reference example 1
The target compound (11.00 g) was obtained as a solid by the same procedure as in 6. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (3H, t, J =
7Hz); 1.26 (3H, t, J = 7Hz); 1.20-2.20 (2H, m); 3.88 (2H,
t, J = 6.5Hz); 4.21 (2H, q, J = 7Hz); 6.24 (1H, d, J = 16Hz);
6.85 (2H, dm, J = 8Hz); 7.44 (2H, dm, J = 8Hz); 7.62 (1H, d, J =
16Hz).

[0449]

Reference Example 18 Using ( E) -3,4-dipropoxycinnamate ethyl (E) -3,4-dihydroxycinnamate (10.41 g) and propyliodide (20.40 g), the same as Reference Example 17 was used. The reaction was carried out to obtain the target compound (10.20 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.02 (6H, t, J =
7Hz); 1.32 (3H, t, J = 7Hz); 1.50-2.20 (4H, m); 3.99 (4H,
t, J = 7Hz); 4.26 (2H, q, J = 7Hz); 6.30 (1H, d, J = 16Hz); 6.7
0-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0450]

Reference Example 19 ( E) -4-Ethoxy-3-methoxyethyl cinnamate (E) -4-Hydroxy-3-methoxycinnamate (5.83 g) and ethyl iodide (5.61 g) were used as a reference example. The same reaction as in 17 was carried out to obtain the target compound (5.55 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.30 (3H, t, J =
7Hz); 1.44 (3H, t, J = 7Hz); 3.89 (3H, s); 4.14 (2H, q, J = 7H
z); 4.24 (2H, q, J = 7Hz); 6.30 (1H, d, J = 16Hz); 6.75-7.35
(3H, m); 7.66 (1H, d, J = 16Hz).

[0451]

Reference Example 20 Ethyl ( E) -3-methoxy-4-propoxycinnamate (E) -4-Hydroxy-3-methoxyethyl cinnamate (11.11 g)
And propyl iodide (10.20 g) were used to carry out the same reaction as in Reference Example 17 to obtain the target compound (12.08 g). NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7Hz); 1.30 (3H, t, J = 7Hz); 1.50-2.20 (2H, m); 3.88 (3H,
s); 3.98 (2H, t, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.28 (1H, d,
J = 16Hz); 6.70-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0452]

[Reference Example 21] ( E) -4-Butoxy-3-ethyl methoxycinnamate (E) -4-Hydroxy-3-methoxyethyl cinnamate (6.66 g) and butyl iodide (6.62 g) were used. The same reaction as in 17 was carried out to obtain the target compound (7.00 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.96 (3H, t, J =
7Hz); 1.30 (3H, t, J = 7Hz); 1.20-2.10 (4H, m); 3.88 (3H,
s); 4.03 (3H, t, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.28 (1H, d,
J = 16Hz); 6.75-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0453]

[Reference Example 22] 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] piperazine Using the compound of Reference Example 4-73 (5.65 g), the same reaction and purification as in Reference Example 12 were carried out to obtain the target compound (6.37 g) as a powder. Melting point: 108-110 ° C NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.75 (1H,
s); 2.35-2.45 (2H, m); 2.65-2.75 (2H, m); 3.25-3.35 (2
H, m); 3.45-3.55 (2H, m); 3.82 (3H, s); 6.28 (1H, s), 6.86
(2H, dm, J = 8.79Hz), 7.16-7.36 (6H, m). Elemental analysis value (as C ₂₀ H ₂₁ ClN ₂ O ₂ ) Calculated value: C; 67.32, H; 5.93, N; 7.85, Cl Measured value: C; 67.09, H; 5.81, N; 7.81, Cl; 10.10.

[0454]

Reference Example 23 4-acetoxy-3,5-dimethoxybenzoic acid 3,5-dimethoxy-4-hydroxybenzoic acid (3.00 g) and acetic anhydride (30 ml) were ice-cooled in a mixture, and pyridine (15 ml) was added. 5
It was dripped over a period of minutes. After stirring at room temperature for 30 minutes, the reaction solution was poured into water and stirred at room temperature for 30 minutes. Extract three times with ethyl acetate, wash the extract with 10% hydrochloric acid, then dry,
Concentrated. The residue was recrystallized from methylene chloride-hexane to obtain the target compound (3.13 g). Melting point: 192-194 ° C. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.
36 (3H, s); 3.90 (6H, s); 7.4
0 (2H, s). Elemental analysis value (as C ₁₁ H ₁₂ O ₆ ) calculated value: C; 55.00, H; 5.04. Measured value: C; 55.02, H; 5.04.

[0455]

[Reference Example 24] Sodium ethyl 3,5-dichlorocinnamate (0.84 g, 55% mineral oil suspension) was added to a mixture of tetrahydrofuran (40 ml) and diethyl phosphonoethyl acetate (4.33 g) in tetrahydrofuran (20 ml). ml) solution was added dropwise under ice cooling at 6-12 ° C over 12 minutes. 30 at room temperature
After stirring for 3 minutes, 3,5-dichlorobenzaldehyde (3.07
a solution of g) in tetrahydrofuran (20 ml) under ice cooling (8-11
(° C) was added dropwise over 10 minutes. After stirring at room temperature for 4 hours, the reaction solution was poured into water and extracted twice with ethyl acetate.
The extract was washed with water, dried and concentrated, and the residue was washed with silica gel (1
Flash column chromatography using 00 g). Fractions eluted with hexane-ethyl acetate (99: 1) were collected to obtain the target compound (3.33 g). Mp: 71-73 ° C. (cold hexane) NMR spectra _{(270MHz, CDCl 3) δ ppm} : 1.34 (3H, t,
J = 7.32Hz); 4.27 (2H, q, J = 7.32Hz); 6.43 (1H, d, J = 16.11H
z); 7.36 (1H, t, J = 1.95Hz); 7.38 (2H, d, J = 1.95Hz); 7.54
(1H, d, J = 16.11Hz) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1770, 164
0, 1580, 1560, 1415, 1360, 1310, 1280, 1270, 1170,
1020, 970, 845. Mass spectrum (m / z): 244 (M ⁺ , ³⁵ Cl); 216; 199; 171. Elemental analysis value (as C ₁₁ H ₁₀ O ₂ Cl ₂ ) calculated value: C; 53.90, H; 4.11, Cl; 28.93. Found: C; 54.01, H; 4.16, Cl; 28.76.

[0456]

[Reference Example 25] The target compound (12.17 g) was obtained in the same manner as in Reference Example 24 using ethyl 2,5-dichlorocinnamate 2,5-dichlorobenzaldehyde (9.74 g). Mp: 34-36 ° C. NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.35 (3H, t,
J = 7.32Hz); 4.29 (2H, q, J = 7.32Hz); 6.42 (1H, d, J = 16.12H
z); 7.27 (1H, dd, J = 8.31,2.44Hz); 7.35 (1H, d, J = 8.30H
z); 7.59 (1H, d, J = 2.44Hz); 7.99 (1H, d, J = 16.12Hz). Mass spectrum (m / z): 244 (M ⁺ , ³⁵ Cl); 209; 199. Elemental analysis Value (as C ₁₁ H ₁₀ O ₂ Cl ₂ ) Calculated: C; 53.90, H; 4.11, Cl; 28.93. Found: C; 54.14, H; 4.24, Cl; 28.77.

[0457]

Reference Example 26 The target compound (23.46 g) was obtained in the same manner as in Reference Example 24 using ethyl 2,3-dichlorocinnamate 2,3-dichlorobenzaldehyde (20.00 g). Melting point: 69-70 ° C. (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.35 (3H, t,
J = 7.32Hz); 4.29 (2H, q, J = 7.32Hz); 6.41 (1H, d, J = 16.12H
z); 7.22 (1H, dd, J = 8.30,8.30Hz); 7.48 (1H, dd, J = 8.30,
1.47Hz); 7.51 (1H, dd, J = 8.30,1.47Hz); 8.08 (1H, d, J = 1
Mass spectrum (m / z): 244 (M ⁺ , ³⁵ Cl); 209; 199. Elemental analysis value (as C ₁₁ H ₁₀ O ₂ Cl ₂ ) calculated value: C; 53.90, H; 4.11, Cl; 28.93. Found: C; 54.10, H; 4.31, Cl; 28.65.

[0458]

Reference Example 27 A reaction was carried out in the same manner as in Reference Example 24 using ethyl 3,5-dimethylcinnamate 3,5-dimethylbenzaldehyde (11.44 g). The crude product was subjected to flash column chromatography using silica gel (300 g), and the fractions eluted with hexane-ethyl acetate (9: 1) were collected to obtain the target compound (15.22 g) as an oil. It was NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.33 (3H, t,
J = 7.32Hz); 2.33 (6H, s); 4.26 (2H, q, J = 7.32Hz); 6.41 (1
H, d, J = 16.12Hz); 7.02 (1H, br.s); 7.14 (2H, br.s); 7.63
Mass spectrum (m / z): 204 (M ⁺ ); 189; 175; 159. Elemental analysis value (as C ₁₃ H ₁₆ O ₂ ) calculated value: C; 76.44, (1H, d, J = 16.12Hz). H; 7.90. Found: C; 76.67, H; 8.14.

[0459]

Reference Example 28 1- [Z-3- (3,5-dichlorophenyl) -3- (4-methoxyphenyl)
A) Acryloyl] piperazine Using the compound of Reference Example 4-127 (1,000 g), Reference Example 1
The reaction and purification were performed in the same manner as in 2, and the indicated compound (1.073
g) was obtained as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.89 (1H,
s); 2.45-2.65 (2H, m); 2.65-2.85 (2H, m); 3.25-3.45 (2H,
m); 3.45-3.65 (2H, m); 3.83 (3H, s); 6.33 (1H, s); 6.87 (2
H, dm, J = 8.79H _Z ); 7.17 (2H, d, J = 1.95H _Z ); 7.19 (2H, dm, J =
8.79H _Z ); 7.35 (1H, t, J = 1.95H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1565, 1515, 1465, 1445, 1250, 1180. Mass spectrum (m / z): 390 (M ⁺ , ³⁵ Cl); 305; 85. Elemental analysis value (as C ₂₀ H ₂₀ Cl ₂ N ₂ O ₂ ) Calculated value: C; 61.39, H; 5.15, N; 7.16, Cl; 18.12. Actual value: C; 61.44, H; 5.39, N; 7.04, Cl; 17.93.

[0460]

Reference Example 29 dl-5- (N-phthaloylaminomethyl) -2-pyrrolidone Saijo et al. [Chem. Pharm. Bull., 5 , 1449 (198
0)], synthesized dl-5-hydroxymethyl-2-pyrrolidone (33.63 g), phthalimide (51.57 g) and triphenylphosphine (91.91 g) in tetrahydrofuran (600
ml) solution, diethyl azodicarboxylate (61.05 g, 0.
A solution of 350 mol) in tetrahydrofuran (80 ml) was added at room temperature. After stirring at room temperature for 1 hour, the reaction solution was concentrated to dryness. The residue was subjected to column chromatography using silica gel (1000 g), ethyl acetate-methanol (1: 0-9: 1).
The fractions eluted in the above were collected, and 62.55 g (8
8%) was obtained as white needle crystals. Mp: 178.0-180.0 ℃ - NMR spectrum (methylene chloride recrystallized from ethyl _{acetate) (270MH Z, CDCl 3)} δ ppm: 1.85-2.05
(1H, m); 2.20-2.40 (3H, m); 3.73 (1H, dd, J = 13.68,5.37
H _Z ); 3.88 (1H, dd, J = 13.68,4.88H _Z ); 3.95-4.05 (1H, m);
6.05 (1H, br.s); 7.70-7.90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3450, 178
0, 1720, 1705, 1495. Mass spectrum (m / z): 245 (M ⁺ +1); 160; 84. Elemental analysis value (as C ₁₃ H ₁₂ N ₂ O ₃ ) Calculated value: C; 63.93, H ; 4.95, N; 11.47. Found: C; 63.65, H; 4.69, N; 11.17.

[0461]

Reference Example 30 (S) -5- (N-phthaloylaminomethyl) -2-pyrrolidone Silverman et al. [J. Org. Chem., 45 , 815 (1980)]
L-pyroglutamic acid ethyl ester synthesized from L-glutamic acid according to the method of Saijo et al. [Chem.Pharm.
ull., 5 , 1449 (1980)] to give (S) -5-hydroxymethyl-2-pyrrolidone. With this compound,
The same operation as in Reference Example 1 was carried out to obtain the title compound as white needle crystals. Melting point: 190.0-191.0 ° C (reconstituted from methylene chloride-ethyl acetate) [α] _D ²⁵ + 3.24 ° (C = 1.08, CHCl ₃ ). Elemental analysis value (as C ₁₃ H ₁₂ N ₂ O ₃ ) Calculated value: C; 63.93, H; 4.95, N; 1
1.47. Found: C; 64.00, H; 4.91, N; 11.57.

[0462]

Reference Example 31 Starting from (R) -5- (N-phthaloylaminomethyl) -2-pyrrolidone D-glutamic acid, the same as Reference Example 30,
The title compound was obtained as white needle crystals. Melting point: 191.0-192.0 ° C (reconstituted from methylene chloride-ethyl acetate) [α] _D ²⁵ -3.23 ° (C = 1.02, CHCl ₃ ). Elemental analysis value (as C ₁₃ H ₁₂ N ₂ O ₃ ) calculated value: C; 63.93, H; 4.95, N; 11.47. Found: C; 64.19, H; 4.87, N; 11.47.

[0463]

Reference Example 32 dl-5- (N-phthaloylaminomethyl) -1- (2-tetrahydro
Pyranyloxyethyl) -2-pyrrolidone sodium hydride (55% mineral oil suspension, 12.29 g) in a mixture of dimethylformamide (600 ml) under ice cooling (5-8 ° C). A solution of the compound (62.52 g) in dimethylformamide (600 ml) was added dropwise. After stirring at room temperature for 30 minutes, 2-tetrahydropyranyloxyethyl bromide (58.
96 g) in dimethylformamide (100 ml) under ice cooling (5
(° C). After stirring at room temperature for 4 hours, the reaction solution was poured into ice water (2 l) and extracted with ethyl acetate three times. The extracts are combined, dried and concentrated, and the resulting residue is purified by silica gel.
It was subjected to column chromatography using (700 g).
Fractions eluting with hexane-ethyl acetate (1: 1-0: 1) were collected to give 53.11 g (56%) of the title compound as a viscous oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.45-1.90
(6H, m); 1.90-2.50 (4H, m); 3.33-3.67 (3H, m); 3.75-4.0
0 (5H, m); 4.08-4.20 (1H, m), 4.58-4.63 (1H, m); 7.70-7.
90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1775, 172
0, 1680, 1490. Mass spectrum (m / z): 373 (M ⁺ +1); 372 (M ⁺ ); 287; 271;
128.

[0464]

[Reference Example 33] (S) -5- (N-phthaloylaminomethyl) -1- (2-tetrahydr
Lopyranyloxyethyl) -2-pyrrolidone Starting from the compound of Reference Example 30, the same procedure as in Reference Example 32 gave the title compound as a viscous oil.

[0465]

Reference Example 34 (R) -5- (N-phthaloylaminomethyl) -1- {2- (2-tetrahi
Doropyranyloxy) ethyl} -2-pyrrolidone Starting from the compound of Reference Example 31, the same procedure as in Reference Example 32 gave the title compound as a viscous oil.

[0466]

[Reference Example 35] dl-1- (2-hydroxyethyl) -5- (N-phthaloylamine
Til ) -2-Pyrrolidone The compound of Reference Example 32 (53.05 g) was added to acetic acid (300 ml) and water.
It was dissolved in a mixture of (150 ml) and stirred at room temperature for 15 hours.
Acetic acid and water were distilled off under reduced pressure, and the obtained oily residue was subjected to column chromatography using silica gel (600 g). Fractions eluted with methylene chloride-methanol (5: 95-7: 93) were pooled to give 32.75 g (80%) of the title compound.
%) As white crystals. Mp: 121.0-123.0 ℃ (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.98-2.55
(4H, m); 3.11 (1H, br.s); 3.40-3.50 (1H, m); 3.70-3.95 (5
H, m); 3.95-4.05 (1H, m); 7.70-7.90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1670, 1495. Mass spectrum (m / z): 289 (M ⁺ +1);
288 (M ⁺ ); 257; 128.

[0467]

Reference Example 36 (S) -1- (2-hydroxyethyl) -5- (N-phthalo
Ilaminomethyl) -2-pyrrolidone Starting from the compound of Reference Example 33, the title compound was obtained as white crystals in the same manner as in Reference Example 35. Melting point: 132.0-133.0 ° C (reconstituted from methylene chloride-hexane) [α] _D ²⁵ -43.4 ° (C = 1.01, CHCl ₃ ). Elemental analysis value (as C ₁₅ H ₁₆ N ₂ O ₄ ) Calculated value: C ; 62.49, H; 5.59, N; 9.72. Actual value: C; 62.66, H; 5.51, N; 9.75.

[0468]

[Reference Example 37] (R) -1- (2-hydroxyethyl) -5- (N-phthaloylamino)
Methyl) -2-pyrrolidone Starting from the compound of Reference Example 34, and in the same manner as in Reference Example 35, the title compound was obtained as white crystals. Melting point: 131.0-133.0 ° C (reconstituted from methylene chloride-hexane) [α] _D ²⁵ + 43.1 ° (C = 1.03, CHCl ₃ ). Elemental analysis value (as C ₁₅ H ₁₆ N ₂ O ₄ ) Calculated value: C ; 62.49, H; 5.59, N; 9.72. Actual value: C; 62.59, H; 5.58, N; 9.73.

[0469]

[Reference Example 38] dl-5-aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
Don The compound of Reference Example 35 (32.59 g) was suspended in ethanol (500 ml), n-butylamine (67 ml) was added, and the mixture was heated with stirring at 80 ° C. for 24 hours. The solvent was evaporated and the obtained residue was subjected to column chromatography using silica gel (300 g). Methylene chloride-methanol-water (9: 1: 0-60: 3
5: 5) and the fractions eluted at 5.70 g
(88%) was obtained as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.40-2.00
(3H, br.s); 1.75-1.93 (1H, m); 2.12-2.27 (1H, m); 2.32-
2.57 (2H, m); 2.88 (1H, dd, J = 13.18,3.91H _Z ); 3.02 (1H, d
d, J = 13.18,4.89H _Z ); 3.37 (1H, ddd, J = 14.16,7.81,2.98
H _Z ); 3.56 (1H, ddd, J = 14.16,5.85,2,93H _z ); 3.70 (1H, dd
d, J = 11.71,5.85,2.93H _Z ); 3.65-3.75 (1H, m); 3.91 (1H, d
dd, J = 11.71,7.81,2.93H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 167
0. Mass spectrum (m / z): 159 (M ⁺ +1); 128.

[0470]

Reference Example 39 (S) -5-Aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
Starting from the compounds of Don Reference Example 36 and following the procedure of Reference Example 38 to give the title compound as an oil. [Α] _D ²⁵ -32.7 ° (C = 1.06, CHCl ₃ ).

[0471]

Reference Example 40 (R) -5-Aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
Starting from the compounds of Don Reference Example 37 and following the procedure of Reference Example 38 to give the title compound as an oil. [Α] _D ²⁵ + 32.3 ° (C = 1.07, CHCl ₃ ).

[0472]

Reference Example 41 dl-octahydropyrrolo [1,2-a] pyrazin-6-one A solution of the compound of Reference Example 38 (15.59 g) and triphenylphosphine (51.67 g) in tetrahydrofuran (280 ml) was added,
A solution of diethyl azodicarboxylate (34.31 g) in tetrahydrofuran (40 ml) was added at room temperature. After stirring at room temperature for 1 hour, the reaction solution was concentrated and dried. Silica gel (260
g) was used for column chromatography, and the fractions eluted with methylene chloride methanol (95: 5-60: 35) were collected to give 8.012 g (58%) of the title compound as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.58 (1H, dd
dd, J = 12.69,9.77,9.77,7.32H _Z ); 1.99 (1H, br.s); 2.16
(1H, dddd, J = 12.69,7.32,7.32,5.37H _Z ); 2.32-2.45 (3H,
m); 2.60 (1H, ddd, J = 11.72,11.72,3.41H _Z ); 2.75-2.90 (1
H, m); 2.97-3.06 (1H, m); 3.16 (1H, dd, J = 11.72,3.90H _Z );
3.55 (1H, dddd, J = 10.75,7.32,7.32,3.90H _Z ); 3.97-4.06
(1H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3350, 168
5. Mass spectrum (m / z): 140 (M ⁺ ); 98.

[0473]

Reference Example 42 (S) -Octahydropyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 39, the title compound was obtained as an oil in the same manner as in Reference Example 41. [Α] _D ²⁵ -25.8 ° (C = 1.28, CHCl ₃ ).

[0474]

Reference Example 43 (R) -Octahydropyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 40, the title compound was obtained as an oil in the same manner as in Reference Example 41. [Α] _D ²⁵ + 25.2 ° (c = 1.35, CHCl ₃ ).

[0475]

[Reference Example 44] dl-2- (3,4,5-trimethoxybenzoyl) octahydropi
Lolo [1,2-a] pyrazin-6-one The compound of Reference Example 41 (2.023 g) in tetrahydrofuran (1
0 ml) solution, sodium bicarbonate (2.425 g) and water (20
ml) was added, and then 3,4,5-trimethoxybenzoyl chloride (3.986 g) in tetrahydrofuran (10 ml) was added dropwise. After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted with methylene chloride three times. The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine,
Dried and concentrated. The residue was subjected to column chromatography using silica gel (200 g), and the fractions eluted with methylene chloride-methanol (1: 0-98: 2) were collected to give 3.37 g (70%) of the title compound as a powder. Obtained. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.55-1.75
(1H, m); 2.15-2.35 (1H, m); 2.40-2.50 (3H, m); 2.55-2.7
5 (1H, m); 2.75-3.10 (3H, m); 3.50-3.70 (1H, m); 3.88 (9
H, s); 4.00-4.20 (1H, m); 6.63 (2H, s). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1680, 163
0, 1585, 1460, 1420, 1330, 1220, 1130. Mass spectrum (m / z): 334 (M ⁺ ); 237; 195.

[0476]

Reference Example 45 (S) -2- (3,4,5-trimethoxybenzoyl) octahydro
The indicated compound was obtained as a powder from the compound of Pyrrolo [1,2-a] pyrazin-6-one Reference Example 42 in the same manner as in Reference Example 44. [Α] _D ²⁵ -15.5 ° (C = 1.08, CHCl ₃ ).

[0477]

Reference Example 46 (R) -2- (3,4,5-trimethoxybenzoyl) octahydro
The indicated compound was obtained as a powder from the compound of Pyrrolo [1,2-a] pyrazin-6-one Reference Example 43 in the same manner as in Reference Example 44. [Α] _D ²⁵ +15.1 ° (C = 1.08, CHCl ₃ ).

[0478]

[Reference Example 47] dl-6- (N- phthaloylaminomethyl ) -2-piperidone Method by Szirtes et al. [J. Med. Chem., 29 , 1654 (1986)]
Dl-pyrro-2-aminoadipic acid (36.
0 g) was reduced by the method of Saijo et al. To give dl-6-hydroxymethyl-2-piperidone (26.71 g). Mp: 81-83 ° C. - NMR spectrum (methylene chloride recrystallized from ethyl _{acetate) (270MH Z, CDCl 3)} δ ppm: 1.28-1.42
(1H, m); 1.65-2.00 (3H, m); 2.20-2.46 (2H, m); 3.45 (1H,
dd, J = 10.25,8.30H _Z ); 3.68 (1H, dd, J = 10.25,2.44H _Z ); 3.
88 (1H, br.s); 7.18 (1H, br.s) Elemental analysis (C ₆ H ₁₁ NO ₂₎ Calculated values:. C; 55.80, H; 8.58, N; 10.84 Found:. C; 55.60, H; 8.39, N; 10.77. Using the above compound (3.06 g) and in the same manner as in Reference Example 29, the title compound (4.59 g, 75%) was obtained as white crystals. Mp: 197-199 ° C. (chloroform - hexane to) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.40-1.60
(1H, m); 1.60-1.80 (1H, m); 1.85-2.05 (2H, m); 2.20-2.4
2 (2H, m); 3.65-4.90 (3H, m); 6.13 (1H, br.s); 7.70-7.90
(4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1680, 1490. Mass spectrum (m / z): 259 (M ⁺ +1); 258 (M ⁺ ); 160; 98.

[0479]

[Reference Example 48] dl-1- (2-hydroxyethyl) -6- (N-phthaloylamine
Cyl) -2-piperidone Using the compound of Reference Example 47 (35.62 g) and in the same manner as in Reference Example 32 and Reference Example 35, the title compound (16.74 g) was obtained as an oil. Yield: 40% (two steps) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.45-2.62
(6H, m); 3.40-4.05 (8H, m); 7.70-7.90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1650, 1620, 1495. Mass spectrum (m / z): 303 (M ⁺ +1);
285; 142.

[0480]

Reference Example 49 dl-6-aminomethyl-1- (2-hydroxyethyl) -2
Using the compound of Piperidone Reference Example 48 (16.69 g) and in the same manner as Reference Example 38, 6.94 g (73%) of the title compound was obtained as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.66-2.00
(4H, m); 1.95-2.25 (3H, br.s); 2.37-2.48 (2H, m); 2.85-
2.95 (2H, m); 3.35-3.45 (1H, m); 3.53 (1H, ddd, J = 14.16,
6.83,3.42H _Z ); 3.63 (1H, ddd, J = 14.16,5.86,3.42H _Z ); 3.
74 (1H, ddd, J = 11.23,5.86,3.42H _Z ); 3.87 (1H, ddd, J = 11.2
3,6.83,3.42H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3380, 161
5. Mass spectrum (m / z): 173 (M ⁺ +1); 155; 142.

[0481]

Reference Example 50 dl-octahydro-2H-pyrido [1,2-a] pyrazin-6-one Using the compound of Reference Example 49 (6.91 g), operating in the same manner as in Reference Example 41, 4.01 g (65%) of compound was obtained as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.35-1.50
(1H, m); 1.60-1.77 (1H, m); 1.77-2.03 (2H, m); 2.10-2.4
0 (1H, br.s); 2.25-2.77 (5H, m); 2.93-3.12 (2H, m); 3.28-
3.45 (1H, m); 4.60-4.75 (1H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3350, 162
5. Mass spectrum (m / z): 154 (M ⁺ ); 112.

[0482]

[Reference Example 51] dl-2- (3,4,5-trimethoxybenzoyl) octahydro-2
H-pyrido [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 50 (3.98 g) and operating as in Reference Example 44, 6.17 g (69%) of the title compound
Was obtained as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.40-2.15
(6H, m); 2.28-2.83 (4H, m); 2.90-3.20 (1H, m); 3.32-3.5
0 (1H, m); 3.87 (9H, s); 4.63-4.80 (1H, m); 6.63 (2H, s). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 158
5, 1460, 1410, 1330, 1125. Mass spectrum (m / z): 348 (M ⁺ ); 237; 195; 153.

[0483]

Reference Example 52 dl- (Z) -7- (3,4-dimethoxyphenyl) methylene-2- (3,4,
5-trimethoxy) benzoyl octahydro-2H-pyrido
[1,2-a] Pyrazin -6-one Using the compound of Reference Example 51 (447.8 mg) and 3,4-dimethoxybenzaldehyde (234.9 mg), the same operation as in Example 29 was carried out. Crude product is a row bar column (B column)
The low polarity fractions eluted with ethyl acetate were collected to give the title compound (41.6 mg) as white crystals. . Yield: 6.5% (2 steps) mp: 73.0-76.0 ° C. (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.60-1.85
(1H, m); 2.10-2.33 (1H, m); 2.50-2.90 (6H, m); 2.90-3.2
0 (1H, m); 3.40-3.60 (1H, m); 3.88 (9H, s); 3.89 (6H, s);
4.65-4.85 (1H, m); 6.60 (1H, s); 6.64 (2H, s); 6.81 (1H,
d, J = 8.06H _Z ); 7.14 (1H, dd, J = 8.06,1.83H _Z ); 7.38 (1H, d,
J = 1.83H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1625, 158
5, 1510, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 496 (M ⁺ ); 301; 195.

[0484]

Reference Example 53 dl- (E) -7- (3,4-dimethoxyphenyl) methylene-2- (3,4,
5-trimethoxy) benzoyl octahydro-2H-pyrido
[1,2-a] Pyrazin-6-one After eluting the compound of Reference Example 52, the elution was further continued to collect highly polar fractions to obtain the title compound (525.3 mg) as white crystals. It was . Yield: 82.3% (2 steps) mp: 166.0-168.0 ° C. (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.45-1.70
(1H, m); 1.90-2.20 (1H, m); 2.45-3.30 (7H, m); 3.50-3.7
0 (1H, m); 3.880 (3H, s); 3.884 (9H, s); 3.91 (3H, s); 4.6
5-4.85 (1H, m); 6.65 (2H, s); 6.87 (1H, dd, J = 1.83H _Z ); 6.
88 (1H, d, J = 8.43H _Z ); 6.95 (1H, dd, J = 8.43,1.83H _Z ); 7.75
(1H, s). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1625, 158
5, 1510, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 496 (M ⁺ ); 301; 195.

[0485]

[Production Example 1] (Tablets) Mix everything except magnesium stearate for 30 minutes,
Magnesium stearate was added through a screen. The mixture was mixed for a further 5 minutes and compressed into tablets with a diameter of 8 mm.

[0486]

[Production Example 2] (Capsule) The mixture was mixed for 5 minutes and filled in a No. 3 capsule.

[0487]

[Production Example 3] (Granule) Mix the above 3 kinds and add 10 of hydroxypropyl cellulose.
Moistened with aqueous solution. It was granulated with a cylindrical condyle machine according to a conventional method, dried at 60 ° C., and sized with a No. 16 sieve.

[0488]

[Production Example 4] (Suppository) The compound was dispersed in a Witopsol base at 50 ° C., and the mixture was cast into a mold for production.

[0489]

[Production Example 5] (Syrup) per 100 ml Compound of Example 3 1 g White sugar 50 Carboxymethylcellulose sodium 0.25 Citric acid 0.15 Sodium citrate 1 Benzoic acid 0.5 Purified water 100 ml White sugar, citric acid, sodium citrate, benzoic acid Was dissolved in purified water, and sodium carboxymethyl cellulose and the compound were dispersed therein. Adjust the liquid volume with purified water,
A syrup was manufactured.

[0490]

[Production Example 6] (Injection) Compound of Example 3 1 mg Polyethylene glycol 150 Polysorbate 80 0.5 Sodium dihydrogen phosphate (dihydrate) 1.6 Sodium monohydrogen phosphate (anhydrous) 1.4 Purified water for injection 1 ml Compound Glycol and polysorbate 8
0 and mixed with purified water for injection. Sodium dihydrogen phosphate (dihydrate) and sodium monohydrogen phosphate (anhydrous) were dissolved in this to adjust the liquid volume. The ampoule was filled, sealed, and sterilized at 121 ° C. for 20 minutes.

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] August 2, 1991

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] 0237

[Correction method] Change

[Correction content]

[0237]

Example 18 1- [3,3-bis (4-methoxyphenyl) thioacryloyl
]]-4- (3,4,5-Trimethoxythiobenzoyl) piperazide
The title compound (0.792 g) was obtained as a yellow powder in the same manner as in Example 16 using the compound of Example 17 (0.790 g). NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.99,3.46,
3.56,3.72,4.27,4.37 (8H, br.s × 6); 3.82,3.83,3.85 (15
H, s × 3); 6.39,6.46 (2H, s × 2); 6.51,6.55 (1H, s × 2);
. 6.80-6.95 (4H, m); 7.10-7.37 (4H, m) Mass spectrum (m / z): 578 ( M +); 545; 513; 367. Infrared absorption spectrum ν _max (CHCl ₃₎ cm ^{- 1} : 1605, 158
0, 1510, 1460, 1425, 1335, 1280, 1170, 1125. Elemental analysis value (as C ₃₁ H ₃₄ N ₂ O ₅ S ₂ ) Calculated value: C; 69.34, H; 5.92, N; 4.84, S; 11.08 Actual value: C; 64.21, H; 6.19, N; 4.64, S; 10.98.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Name of item to be corrected] 0444

[Correction method] Change

[Correction content]

[0444]

[Reference Example 13] (Z)-and (E) -3-phenyl-3- (2-naphthyl) acrylic acid
Using Chill 2-naphthyl phenyl ketone (10.10 g), Reference Example 1
The same reaction as in the first half was performed. The crude product was treated with silica gel (2
Column chromatography using 00 g) and Lobar-
Subjected to medium pressure liquid chromatography using a C column. Fractions eluted with hexane-ethyl acetate were collected,
The Z-isomer (2.48 g) was obtained. Melting point: 91-92 ° C (hexane) Elution was continued with the same solvent to obtain an E-isomer (4.44 g). Melting point: 84-85 ° C (hexane)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Internal reference number FI Technical indication C07D 487/04 140 7019-4C // A61K 31/435 7252-4C 31/495 7252-4C (72 ) Inventor Masaaki Miyamoto 1-258 Hiromachi, Shinagawa-ku, Tokyo Sankyo stock company (72) Inventor Yasuki Iijima 1-2-2 Hiromachi, Shinagawa-ku, Tokyo Sankyo stock company

Claims (2)

[Claims] 1. A general formula: {In the formula, R ¹ and R ² are the same or different, and a group having the formula -R ⁶ [in the formula, R ⁶ is an optionally substituted aryl group (the substituents are the following group A; 1 to 5 substituents selected from the above) or an optionally substituted heteroaryl group (the substituents are 1 to 5 substituents selected from the following Group A). Indicates. ], A group having the formula —CH═CH—R ⁶ (wherein R ⁶ has the same meaning as described above), or a formula
A group having —C≡C—R ⁶ (in the formula, R ⁶ has the same meaning as described above). R ³ is a hydrogen atom, a lower alkyl group,
A cyano group or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as defined above), or, together with R ⁵ , has the general formula — (CH ₂ ) _p — (formula In the formula, p represents 1 to 3.). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituents are 1 to 5 substituents selected from the following Group A and Group B) or an optionally substituted heteroaryl group. (The substituent is
It is 1 to 5 substituents selected from the following Group A. )
Indicates. R ⁵ represents a hydrogen atom or a lower alkyl group, or, together with R ³ , represents a general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. Provided that R ⁴ represents a 3-pyridyl group, R ³ represents a hydrogen atom or a lower alkyl group, R ⁵ represents a hydrogen atom or a lower alkyl group, and m and n each represent ^1. And R ² are the same or different and each is a group having the formula —R ^{6 ′} , wherein R ^{6 ′} is a substituted aryl group (wherein the substituent is 1 to 5 selected from the following group A). Or a heteroaryl group which may be substituted (the substituents are 1 to 5 substituents selected from the following Group A). ], Expression
Indicating group (wherein, R ⁶ is. As defined above) with a -CH = CH-R ⁶ radical (wherein with or Formula -C≡C -R ^6, R ⁶ is as defined above .) Is shown. } The compound and its salt represented by these. [Group A] Lower alkyl group, halogeno lower alkyl group, lower alkoxy group, hydroxyl group, alkylenedioxy group having 1 to 4 carbon atoms, acyloxy group, halogen atom, cyano group and nitro group. [Group B] Lower alkylsulfonyl group, lower alkylsulfinyl group and lower alkylthio group. 2. A general formula: {In the formula, R ¹ and R ² are the same or different, and a group having the formula -R ⁶ [in the formula, R ⁶ is an optionally substituted aryl group (the substituents are the following group A; 1 to 5 substituents selected from the above) or an optionally substituted heteroaryl group (the substituents are 1 to 5 substituents selected from the following Group A). Indicates. ], A group having the formula —CH═CH—R ⁶ (wherein R ⁶ has the same meaning as described above), or a formula
A group having —C≡C—R ⁶ (in the formula, R ⁶ has the same meaning as described above). R ³ is a hydrogen atom, a lower alkyl group,
A cyano group or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as defined above), or, together with R ⁵ , has the general formula — (CH ₂ ) _p — (formula In the formula, p represents 1 to 3.). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituents are 1 to 5 substituents selected from the following Group A and Group B) or an optionally substituted heteroaryl group. (The substituent is
It is 1 to 5 substituents selected from the following Group A. )
Indicates. R ⁵ represents a hydrogen atom or a lower alkyl group, or, together with R ³ , represents a general formula — (CH ₂ ) _p — (in the formula, p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. } A prophylactic or therapeutic agent for a disease caused by platelet activating factor (PAF), which comprises a compound represented by the formula or a salt thereof. [Group A] Lower alkyl group, halogeno lower alkyl group, lower alkoxy group, hydroxyl group, alkylenedioxy group having 1 to 4 carbon atoms, acyloxy group, halogen atom, cyano group and nitro group. [Group B] Lower alkylsulfonyl group, lower alkylsulfinyl group and lower alkylthio group.